MEDICATION SAFETY ISSUES
Safety issues:
Lipid-based amphotericin formulations (Amphotec®) may be confused with conventional formulations (Amphocin®, Fungizone®)
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Amphotec®
PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral
DOSING: ADULTS
Note: Premedication: For patients who experience chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Usual dosage: I.V.: 3-4 mg/kg/day (infusion of 1 mg/kg/hour); maximum: 7.5 mg/kg/day
A regimen of 6 mg/kg/day has been used for treatment of life-threatening invasive mold infections in immunocompromised patients; maximum: 7.5 mg/kg/day.
Initially infuse at 1 mg/kg/hour. Rate of infusion may be increased with subsequent doses to 3 mg/kg/hour as patient tolerance allows. Treatment should continue as patient tolerance allows, until complete resolution of microbiologic and clinical evidence of fungal disease.
DOSING: PEDIATRIC — Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Amphotec®: 50 mg, 100 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Amphotec®: 50 mg, 100 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Avoid injection faster than 1 mg/kg/hour. For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered. If severe respiratory distress occurs, the infusion should be immediately discontinued.
COMPATIBILITY — Stable in D5W; incompatible with NS.
Y-site administration: Compatible: Acyclovir, aminophylline, cefoxitin, ceftizoxime, clindamycin, dexamethasone sodium phosphate, fentanyl, furosemide, ganciclovir, granisetron, hydrocortisone sodium succinate, ifosfamide, lorazepam, mannitol, methotrexate, methylprednisolone sodium succinate, nitroglycerin, sufentanil, trimethoprim/sulfamethoxazole, vinblastine, vincristine, zidovudine. Incompatible: Alfentanil, amikacin, ampicillin, ampicillin/sulbactam, atenolol, aztreonam, bretylium, buprenorphine, butorphanol, calcium chloride, calcium gluconate, carboplatin, cefazolin, cefepime, cefoperazone, ceftazidime, ceftriaxone, chlorpromazine, cimetidine, cisatracurium, cisplatin, cyclophosphamide, cyclosporine, cytarabine, diazepam, digoxin, diphenhydramine, dobutamine, dopamine, doxorubicin, doxorubicin liposome, droperidol, enalaprilat, esmolol, famotidine, fluconazole, fluorouracil, gatifloxacin, gentamicin, haloperidol, heparin, hydromorphone, hydroxyzine, imipenem/cilastatin, labetalol, leucovorin, lidocaine, magnesium sulfate, meperidine, mesna, metoclopramide, metoprolol, metronidazole, midazolam, mitoxantrone, morphine, nalbuphine, naloxone, ofloxacin, ondansetron, paclitaxel, pentobarbital, phenobarbital, phenytoin, piperacillin, piperacillin/tazobactam, potassium chloride, prochlorperazine, promethazine, propranolol, ranitidine, remifentanil, sodium bicarbonate, ticarcillin, ticarcillin/clavulanate, tobramycin, vancomycin, vecuronium, verapamil, vinorelbine.
USE — Treatment of invasive aspergillosis in patients who have failed amphotericin B deoxycholate treatment, or who have renal impairment or experience unacceptable toxicity which precludes treatment with amphotericin B deoxycholate in effective doses.
USE - UNLABELED / INVESTIGATIONAL — Effective in patients with serious Candida species infections
ADVERSE REACTIONS SIGNIFICANT
>10%: Central nervous system: Chills, fever
1% to 10%:
Cardiovascular: Hypotension, tachycardia
Central nervous system: Headache
Dermatologic: Rash
Endocrine & metabolic: Hypokalemia, hypomagnesemia
Gastrointestinal: Nausea, diarrhea, abdominal pain
Hematologic: Thrombocytopenia
Hepatic: LFT change
Neuromuscular & skeletal: Rigors
Renal: Creatinine increased
Respiratory: Dyspnea
Note: Amphotericin B colloidal dispersion has an improved therapeutic index compared to conventional amphotericin B, and has been used safely in patients with amphotericin B-related nephrotoxicity; however, continued decline of renal function has occurred in some patients.
CONTRAINDICATIONS — Hypersensitivity to amphotericin B or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued. During the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Sometimes severe, usually subside with continued therapy - manage with decreased rate of infusion and pretreatment with antihistamines/corticosteroids.
Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy
Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Excretion in breast milk unknown/contraindicated
BREAST-FEEDING CONSIDERATIONS — Due to limited data, consider discontinuing nursing during therapy.
MONITORING PARAMETERS — Liver function tests, electrolytes, BUN, Cr, temperature, CBC, I/O, signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes)
CANADIAN BRAND NAMES — Amphotec®
INTERNATIONAL BRAND NAMES — Amphocil (AT, AU, BR, CZ, DK, FI, GB, HK, HN, IL, IT, MX, MY, NL, SE, TH, TW)
MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages (Lyman, 1992).
PHARMACODYNAMICS / KINETICS
Distribution: Vd: Total volume increases with higher doses, reflects increasing uptake by tissues (with 4 mg/kg/day = 4 L/kg); predominantly distributed in the liver; concentrations in kidneys and other tissues are lower than observed with conventional amphotericin B
Half-life elimination: 28-29 hours; prolonged with higher दोसेस.
Monday, August 2, 2010
Amphotericin B (conventional)
MEDICATION SAFETY ISSUES
Safety issues:
Conventional amphotericin formulations (Amphocin®, Fungizone®) may be confused with lipid-based formulations (AmBisome®, Abelcet®, Amphotec®).
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral
DOSING: ADULTS — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Test dose: I.V.: 1 mg infused over 20-30 minutes. Many clinicians believe a test dose is unnecessary.
Susceptible fungal infections: I.V.: Adults: 0.05-1.5 mg/kg/day; 1-1.5 mg/kg over 4-6 hours every other day may be given once therapy is established; aspergillosis, rhinocerebral mucormycosis, often require 1-1.5 mg/kg/day; do not exceed 1.5 mg/kg/day
Aspergillosis, disseminated: I.V.: 0.6-0.7 mg/kg/day for 3-6 months
Bone marrow transplantation (prophylaxis): I.V.: Low-dose amphotericin B 0.1-0.25 mg/kg/day has been administered after bone marrow transplantation to reduce the risk of invasive fungal disease.
Candidemia (neutropenic or non-neutropenic): I.V.: 0.5-1 mg/kg/day until 14 days after last positive blood culture and resolution of signs and symptoms (Pappas, 2009)
Candidiasis, chronic, disseminated: I.V.: 0.5-0.7 mg/kg/day for 3-6 months and resolution of radiologic lesions (Pappas, 2009)
Dematiaceous fungi: I.V.: 0.7 mg/kg/day in combination with an azole
Endocarditis: I.V.: 0.6-1 mg/kg/day (with or without flucytosine) for 6 weeks after valve replacement; Note: If isolates susceptible and/or clearance demonstrated, guidelines recommend step-down to fluconazole; also for long-term suppression therapy if valve replacement is not possible (Pappas, 2009)
Endophthalmitis, fungal:
Intravitreal (unlabeled use): 10 mcg in 0.1 mL (in conjunction with systemic therapy)
I.V.: 0.7-1 mg/kg/day (with or without flucytosine) for at least 4-6 weeks (Pappas, 2009)
Esophageal: I.V.: 0.3-0.7 mg/kg/day for 14-21 days after clinical improvement
Histoplasmosis: Chronic, severe pulmonary or disseminated: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8 mg/kg every other day (or 3 times/week) until total dose of 10-15 mg/kg; may continue itraconazole as suppressive therapy (lifelong for immunocompromised patients)
Meningitis:
Candidal: I.V.: 0.7-1 mg/kg/day (with or without flucytosine) for at least 4 weeks; Note: Liposomal amphotericin favored by IDSA guidelines based on decreased risk of nephrotoxicity and potentially better CNS penetration (Pappas, 2009)
Cryptococcal or Coccidioides: I.T.: Initial: 25-300 mcg every 48-72 hours; increase to 500 mcg to 1 mg as tolerated; maximum total dose: 15 mg has been suggested
Histoplasma: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8 mg/kg every other day (or 3 times/week) for 3 months total duration; follow with fluconazole suppressive therapy for up to 12 months
Meningoencephalitis, cryptococcal: I.V.:
HIV positive: 0.7-1 mg/kg/day (plus flucytosine 100 mg/kg/day) for 2 weeks, then change to oral fluconazole for at least 10 weeks; alternatively, amphotericin and flucytosine may be continued uninterrupted for 6-10 weeks
HIV negative: 0.5-0.7 mg/kg/day (plus flucytosine) for 2 weeks
Oropharyngeal candidiasis: I.V.: 0.3 mg/kg/day for 7-14 days (Pappas, 2009)
Osteoarticular candidiasis: I.V.: 0.5-1 mg/kg/day for several weeks, followed by fluconazole for 6-12 months (osteomyelitis) or 6 weeks (septic arthritis)
Penicillium marneffei: I.V.: 0.6 mg/kg/day for 2 weeks
Pneumonia: Cryptococcal (mild-to-moderate): I.V.:
HIV positive: 0.5-1 mg/kg/day
HIV negative: 0.5-0.7 mg/kg/day (plus flucytosine) for 2 weeks
Sporotrichosis: Pulmonary, meningeal, osteoarticular or disseminated: I.V.: Total dose of 1-2 g, then change to oral itraconazole or fluconazole for suppressive therapy
Urinary tract candidiasis (Pappas, 2009):
Fungus balls: I.V.: 0.5-0.7 mg/kg/day with or without flucytosine 25 mg/kg 4 times daily
Pyelonephritis: I.V.: 0.5-0.7 mg/kg/day with or without flucytosine 25 mg/kg 4 times daily for 2 weeks
Symptomatic cystitis: I.V.: 0.3-0.6 mg/kg/day for 1-7 days
Bladder irrigation: Irrigate with 50 mcg/mL solution instilled periodically or continuously for 5-10 days or until cultures are clear for fluconazole-resistant Candida
DOSING: PEDIATRIC — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
(For additional information see "Amphotericin B (conventional): Pediatric drug information")
Test dose: I.V.: Infants and Children: 0.1 mg/kg/dose to a maximum of 1 mg; infuse over 30-60 minutes. Many clinicians believe a test dose is unnecessary.
Susceptible fungal infections: I.V.: Infants and Children: Maintenance dose: 0.25-1 mg/kg/day given once daily; infuse over 2-6 hours. Once therapy has been established, amphotericin B can be administered on an every-other-day basis at 1-1.5 mg/kg/dose; cumulative dose: 1.5-2 g over 6-10 weeks
Note: Duration of therapy varies with nature of infection: Usual duration is 4-12 weeks or cumulative dose of 1-4 g.
Meningitis, coccidioidal or cryptococcal: I.T.: Children: 25-100 mcg every 48-72 hours; increase to 500 mcg as tolerated
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
If renal dysfunction is due to the drug, the daily total can be decreased by 50% or the dose can be given every other day. I.V. therapy may take several months.
Poorly dialyzed; no supplemental dose is necessary when using hemo- or peritoneal dialysis or continuous renal replacement therapy (CRRT).
Administration in dialysate: 1-2 mg/L of peritoneal dialysis fluid either with or without low-dose I.V. amphotericin B (a total dose of 2-10 mg/kg given over 7-14 days). Precipitate may form in ionic dialysate solutions.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as desoxycholate: 50 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — May be infused over 4-6 hours. For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered. Bolus infusion of normal saline immediately preceding, or immediately preceding and following amphotericin B may reduce drug-induced nephrotoxicity. Risk of nephrotoxicity increases with amphotericin B doses >1 mg/kg/day. Infusion of admixtures more concentrated than 0.25 mg/mL should be limited to patients absolutely requiring volume contraction.
COMPATIBILITY
Solution compatibility:
Compatible: Heparin sodium, hydrocortisone, sodium bicarbonate.
Incompatible: Ampicillin, calcium gluconate, carbenicillin, cimetidine, dopamine, gentamicin, lidocaine, potassium chloride, sodium chloride, tetracycline, verapamil.
USE — Treatment of severe systemic and central nervous system infections caused by susceptible fungi such as Candida species, Histoplasma capsulatum, Cryptococcus neoformans, Aspergillus species, Blastomyces dermatitidis, Torulopsis glabrata, and Coccidioides immitis; fungal peritonitis; irrigant for bladder fungal infections; used in fungal infection in patients with bone marrow transplantation, amebic meningoencephalitis, ocular aspergillosis (intraocular injection), candidal cystitis (bladder irrigation), chemoprophylaxis (low-dose I.V.), immunocompromised patients at risk of aspergillosis (intranasal/nebulized), refractory meningitis (intrathecal), coccidioidal arthritis (intra-articular/I.M.).
Low-dose amphotericin B has been administered after bone marrow transplantation to reduce the risk of invasive fungal disease.
ADVERSE REACTIONS SIGNIFICANT
Systemic:
>10%:
Cardiovascular: Hypotension, tachypnea
Central nervous system: Fever, chills, headache (less frequent with I.T.), malaise
Endocrine & metabolic: Hypokalemia, hypomagnesemia
Gastrointestinal: Anorexia, nausea (less frequent with I.T.), vomiting (less frequent with I.T.), diarrhea, heartburn, cramping epigastric pain
Hematologic: Normochromic-normocytic anemia
Local: Pain at injection site with or without phlebitis or thrombophlebitis (incidence may increase with peripheral infusion of admixtures)
Neuromuscular & skeletal: Generalized pain, including muscle and joint pains (less frequent with I.T.)
Renal: Decreased renal function and renal function abnormalities including azotemia, renal tubular acidosis, nephrocalcinosis (>0.1 mg/mL)
1% to 10%:
Cardiovascular: Hypertension, flushing
Central nervous system: Delirium, arachnoiditis, pain along lumbar nerves (especially I.T. therapy)
Genitourinary: Urinary retention
Hematologic: Leukocytosis
Neuromuscular & skeletal: Paresthesia (especially with I.T. therapy)
<1% (Limited to important or life-threatening): Acute liver failure, agranulocytosis, anuria, bone marrow suppression, cardiac arrest, coagulation defects, convulsions, dyspnea, hearing loss, leukopenia, maculopapular rash, renal failure, renal tubular acidosis, thrombocytopenia, vision changes
CONTRAINDICATIONS — Hypersensitivity to amphotericin or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Error prevention: See "Other warnings/precautions" below. Fungal infections: See "Disease-related concerns" below.
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Acute reactions (including fever and chills) may occur 1-3 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses.
Disease-related concerns: Fungal infections: [U.S. Boxed Warning]: Should be used primarily for treatment of progressive, potentially life-threatening fungal infections, not noninvasive forms of infection. Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues: Nephrotoxic drugs: Avoid use with other nephrotoxic drugs; drug-induced renal toxicity usually improves with interrupting therapy, decreasing dosage, or increasing dosing interval.
Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
Other warnings/precautions: Error prevention: [U.S. Boxed warning]: Verify the product name and dosage if dose exceeds 1.5 mg/kg.
DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy
Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Excretion in breast milk unknown/contraindicated
MONITORING PARAMETERS — Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc)
REFERENCE RANGE — Therapeutic: 1-2 mcg/mL (SI: 1-2.2 µmol/L)
CANADIAN BRAND NAMES — Fungizone®
INTERNATIONAL BRAND NAMES — Amphocil (MX); Fungizone (PL); Terix (MX)
MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages (Lyman, 1992).
PHARMACODYNAMICS / KINETICS
Distribution: Minimal amounts enter the aqueous humor, bile, CSF (inflamed or noninflamed meninges), amniotic fluid, pericardial fluid, pleural fluid, and synovial fluid
Protein binding, plasma: 90%
Half-life elimination: Biphasic: Initial: 15-48 hours; Terminal: 15 days
Time to peak: Within 1 hour following a 4- to 6-hour dose
Excretion: Urine (2% to 5% as biologically active form); ~40% eliminated over a 7-day period and may be detected in urine for at least 7 weeks after discontinued उसे.
Safety issues:
Conventional amphotericin formulations (Amphocin®, Fungizone®) may be confused with lipid-based formulations (AmBisome®, Abelcet®, Amphotec®).
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral
DOSING: ADULTS — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Test dose: I.V.: 1 mg infused over 20-30 minutes. Many clinicians believe a test dose is unnecessary.
Susceptible fungal infections: I.V.: Adults: 0.05-1.5 mg/kg/day; 1-1.5 mg/kg over 4-6 hours every other day may be given once therapy is established; aspergillosis, rhinocerebral mucormycosis, often require 1-1.5 mg/kg/day; do not exceed 1.5 mg/kg/day
Aspergillosis, disseminated: I.V.: 0.6-0.7 mg/kg/day for 3-6 months
Bone marrow transplantation (prophylaxis): I.V.: Low-dose amphotericin B 0.1-0.25 mg/kg/day has been administered after bone marrow transplantation to reduce the risk of invasive fungal disease.
Candidemia (neutropenic or non-neutropenic): I.V.: 0.5-1 mg/kg/day until 14 days after last positive blood culture and resolution of signs and symptoms (Pappas, 2009)
Candidiasis, chronic, disseminated: I.V.: 0.5-0.7 mg/kg/day for 3-6 months and resolution of radiologic lesions (Pappas, 2009)
Dematiaceous fungi: I.V.: 0.7 mg/kg/day in combination with an azole
Endocarditis: I.V.: 0.6-1 mg/kg/day (with or without flucytosine) for 6 weeks after valve replacement; Note: If isolates susceptible and/or clearance demonstrated, guidelines recommend step-down to fluconazole; also for long-term suppression therapy if valve replacement is not possible (Pappas, 2009)
Endophthalmitis, fungal:
Intravitreal (unlabeled use): 10 mcg in 0.1 mL (in conjunction with systemic therapy)
I.V.: 0.7-1 mg/kg/day (with or without flucytosine) for at least 4-6 weeks (Pappas, 2009)
Esophageal: I.V.: 0.3-0.7 mg/kg/day for 14-21 days after clinical improvement
Histoplasmosis: Chronic, severe pulmonary or disseminated: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8 mg/kg every other day (or 3 times/week) until total dose of 10-15 mg/kg; may continue itraconazole as suppressive therapy (lifelong for immunocompromised patients)
Meningitis:
Candidal: I.V.: 0.7-1 mg/kg/day (with or without flucytosine) for at least 4 weeks; Note: Liposomal amphotericin favored by IDSA guidelines based on decreased risk of nephrotoxicity and potentially better CNS penetration (Pappas, 2009)
Cryptococcal or Coccidioides: I.T.: Initial: 25-300 mcg every 48-72 hours; increase to 500 mcg to 1 mg as tolerated; maximum total dose: 15 mg has been suggested
Histoplasma: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8 mg/kg every other day (or 3 times/week) for 3 months total duration; follow with fluconazole suppressive therapy for up to 12 months
Meningoencephalitis, cryptococcal: I.V.:
HIV positive: 0.7-1 mg/kg/day (plus flucytosine 100 mg/kg/day) for 2 weeks, then change to oral fluconazole for at least 10 weeks; alternatively, amphotericin and flucytosine may be continued uninterrupted for 6-10 weeks
HIV negative: 0.5-0.7 mg/kg/day (plus flucytosine) for 2 weeks
Oropharyngeal candidiasis: I.V.: 0.3 mg/kg/day for 7-14 days (Pappas, 2009)
Osteoarticular candidiasis: I.V.: 0.5-1 mg/kg/day for several weeks, followed by fluconazole for 6-12 months (osteomyelitis) or 6 weeks (septic arthritis)
Penicillium marneffei: I.V.: 0.6 mg/kg/day for 2 weeks
Pneumonia: Cryptococcal (mild-to-moderate): I.V.:
HIV positive: 0.5-1 mg/kg/day
HIV negative: 0.5-0.7 mg/kg/day (plus flucytosine) for 2 weeks
Sporotrichosis: Pulmonary, meningeal, osteoarticular or disseminated: I.V.: Total dose of 1-2 g, then change to oral itraconazole or fluconazole for suppressive therapy
Urinary tract candidiasis (Pappas, 2009):
Fungus balls: I.V.: 0.5-0.7 mg/kg/day with or without flucytosine 25 mg/kg 4 times daily
Pyelonephritis: I.V.: 0.5-0.7 mg/kg/day with or without flucytosine 25 mg/kg 4 times daily for 2 weeks
Symptomatic cystitis: I.V.: 0.3-0.6 mg/kg/day for 1-7 days
Bladder irrigation: Irrigate with 50 mcg/mL solution instilled periodically or continuously for 5-10 days or until cultures are clear for fluconazole-resistant Candida
DOSING: PEDIATRIC — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
(For additional information see "Amphotericin B (conventional): Pediatric drug information")
Test dose: I.V.: Infants and Children: 0.1 mg/kg/dose to a maximum of 1 mg; infuse over 30-60 minutes. Many clinicians believe a test dose is unnecessary.
Susceptible fungal infections: I.V.: Infants and Children: Maintenance dose: 0.25-1 mg/kg/day given once daily; infuse over 2-6 hours. Once therapy has been established, amphotericin B can be administered on an every-other-day basis at 1-1.5 mg/kg/dose; cumulative dose: 1.5-2 g over 6-10 weeks
Note: Duration of therapy varies with nature of infection: Usual duration is 4-12 weeks or cumulative dose of 1-4 g.
Meningitis, coccidioidal or cryptococcal: I.T.: Children: 25-100 mcg every 48-72 hours; increase to 500 mcg as tolerated
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
If renal dysfunction is due to the drug, the daily total can be decreased by 50% or the dose can be given every other day. I.V. therapy may take several months.
Poorly dialyzed; no supplemental dose is necessary when using hemo- or peritoneal dialysis or continuous renal replacement therapy (CRRT).
Administration in dialysate: 1-2 mg/L of peritoneal dialysis fluid either with or without low-dose I.V. amphotericin B (a total dose of 2-10 mg/kg given over 7-14 days). Precipitate may form in ionic dialysate solutions.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as desoxycholate: 50 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — May be infused over 4-6 hours. For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered. Bolus infusion of normal saline immediately preceding, or immediately preceding and following amphotericin B may reduce drug-induced nephrotoxicity. Risk of nephrotoxicity increases with amphotericin B doses >1 mg/kg/day. Infusion of admixtures more concentrated than 0.25 mg/mL should be limited to patients absolutely requiring volume contraction.
COMPATIBILITY
Solution compatibility:
Compatible: Heparin sodium, hydrocortisone, sodium bicarbonate.
Incompatible: Ampicillin, calcium gluconate, carbenicillin, cimetidine, dopamine, gentamicin, lidocaine, potassium chloride, sodium chloride, tetracycline, verapamil.
USE — Treatment of severe systemic and central nervous system infections caused by susceptible fungi such as Candida species, Histoplasma capsulatum, Cryptococcus neoformans, Aspergillus species, Blastomyces dermatitidis, Torulopsis glabrata, and Coccidioides immitis; fungal peritonitis; irrigant for bladder fungal infections; used in fungal infection in patients with bone marrow transplantation, amebic meningoencephalitis, ocular aspergillosis (intraocular injection), candidal cystitis (bladder irrigation), chemoprophylaxis (low-dose I.V.), immunocompromised patients at risk of aspergillosis (intranasal/nebulized), refractory meningitis (intrathecal), coccidioidal arthritis (intra-articular/I.M.).
Low-dose amphotericin B has been administered after bone marrow transplantation to reduce the risk of invasive fungal disease.
ADVERSE REACTIONS SIGNIFICANT
Systemic:
>10%:
Cardiovascular: Hypotension, tachypnea
Central nervous system: Fever, chills, headache (less frequent with I.T.), malaise
Endocrine & metabolic: Hypokalemia, hypomagnesemia
Gastrointestinal: Anorexia, nausea (less frequent with I.T.), vomiting (less frequent with I.T.), diarrhea, heartburn, cramping epigastric pain
Hematologic: Normochromic-normocytic anemia
Local: Pain at injection site with or without phlebitis or thrombophlebitis (incidence may increase with peripheral infusion of admixtures)
Neuromuscular & skeletal: Generalized pain, including muscle and joint pains (less frequent with I.T.)
Renal: Decreased renal function and renal function abnormalities including azotemia, renal tubular acidosis, nephrocalcinosis (>0.1 mg/mL)
1% to 10%:
Cardiovascular: Hypertension, flushing
Central nervous system: Delirium, arachnoiditis, pain along lumbar nerves (especially I.T. therapy)
Genitourinary: Urinary retention
Hematologic: Leukocytosis
Neuromuscular & skeletal: Paresthesia (especially with I.T. therapy)
<1% (Limited to important or life-threatening): Acute liver failure, agranulocytosis, anuria, bone marrow suppression, cardiac arrest, coagulation defects, convulsions, dyspnea, hearing loss, leukopenia, maculopapular rash, renal failure, renal tubular acidosis, thrombocytopenia, vision changes
CONTRAINDICATIONS — Hypersensitivity to amphotericin or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Error prevention: See "Other warnings/precautions" below. Fungal infections: See "Disease-related concerns" below.
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Acute reactions (including fever and chills) may occur 1-3 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses.
Disease-related concerns: Fungal infections: [U.S. Boxed Warning]: Should be used primarily for treatment of progressive, potentially life-threatening fungal infections, not noninvasive forms of infection. Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues: Nephrotoxic drugs: Avoid use with other nephrotoxic drugs; drug-induced renal toxicity usually improves with interrupting therapy, decreasing dosage, or increasing dosing interval.
Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
Other warnings/precautions: Error prevention: [U.S. Boxed warning]: Verify the product name and dosage if dose exceeds 1.5 mg/kg.
DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy
Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Excretion in breast milk unknown/contraindicated
MONITORING PARAMETERS — Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc)
REFERENCE RANGE — Therapeutic: 1-2 mcg/mL (SI: 1-2.2 µmol/L)
CANADIAN BRAND NAMES — Fungizone®
INTERNATIONAL BRAND NAMES — Amphocil (MX); Fungizone (PL); Terix (MX)
MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages (Lyman, 1992).
PHARMACODYNAMICS / KINETICS
Distribution: Minimal amounts enter the aqueous humor, bile, CSF (inflamed or noninflamed meninges), amniotic fluid, pericardial fluid, pleural fluid, and synovial fluid
Protein binding, plasma: 90%
Half-life elimination: Biphasic: Initial: 15-48 hours; Terminal: 15 days
Time to peak: Within 1 hour following a 4- to 6-hour dose
Excretion: Urine (2% to 5% as biologically active form); ~40% eliminated over a 7-day period and may be detected in urine for at least 7 weeks after discontinued उसे.
Amphotericin B (conventional)
MEDICATION SAFETY ISSUES
Safety issues:
Conventional amphotericin formulations (Amphocin®, Fungizone®) may be confused with lipid-based formulations (AmBisome®, Abelcet®, Amphotec®).
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral
DOSING: ADULTS — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Test dose: I.V.: 1 mg infused over 20-30 minutes. Many clinicians believe a test dose is unnecessary.
Susceptible fungal infections: I.V.: Adults: 0.05-1.5 mg/kg/day; 1-1.5 mg/kg over 4-6 hours every other day may be given once therapy is established; aspergillosis, rhinocerebral mucormycosis, often require 1-1.5 mg/kg/day; do not exceed 1.5 mg/kg/day
Aspergillosis, disseminated: I.V.: 0.6-0.7 mg/kg/day for 3-6 months
Bone marrow transplantation (prophylaxis): I.V.: Low-dose amphotericin B 0.1-0.25 mg/kg/day has been administered after bone marrow transplantation to reduce the risk of invasive fungal disease.
Candidemia (neutropenic or non-neutropenic): I.V.: 0.5-1 mg/kg/day until 14 days after last positive blood culture and resolution of signs and symptoms (Pappas, 2009)
Candidiasis, chronic, disseminated: I.V.: 0.5-0.7 mg/kg/day for 3-6 months and resolution of radiologic lesions (Pappas, 2009)
Dematiaceous fungi: I.V.: 0.7 mg/kg/day in combination with an azole
Endocarditis: I.V.: 0.6-1 mg/kg/day (with or without flucytosine) for 6 weeks after valve replacement; Note: If isolates susceptible and/or clearance demonstrated, guidelines recommend step-down to fluconazole; also for long-term suppression therapy if valve replacement is not possible (Pappas, 2009)
Endophthalmitis, fungal:
Intravitreal (unlabeled use): 10 mcg in 0.1 mL (in conjunction with systemic therapy)
I.V.: 0.7-1 mg/kg/day (with or without flucytosine) for at least 4-6 weeks (Pappas, 2009)
Esophageal: I.V.: 0.3-0.7 mg/kg/day for 14-21 days after clinical improvement
Histoplasmosis: Chronic, severe pulmonary or disseminated: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8 mg/kg every other day (or 3 times/week) until total dose of 10-15 mg/kg; may continue itraconazole as suppressive therapy (lifelong for immunocompromised patients)
Meningitis:
Candidal: I.V.: 0.7-1 mg/kg/day (with or without flucytosine) for at least 4 weeks; Note: Liposomal amphotericin favored by IDSA guidelines based on decreased risk of nephrotoxicity and potentially better CNS penetration (Pappas, 2009)
Cryptococcal or Coccidioides: I.T.: Initial: 25-300 mcg every 48-72 hours; increase to 500 mcg to 1 mg as tolerated; maximum total dose: 15 mg has been suggested
Histoplasma: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8 mg/kg every other day (or 3 times/week) for 3 months total duration; follow with fluconazole suppressive therapy for up to 12 months
Meningoencephalitis, cryptococcal: I.V.:
HIV positive: 0.7-1 mg/kg/day (plus flucytosine 100 mg/kg/day) for 2 weeks, then change to oral fluconazole for at least 10 weeks; alternatively, amphotericin and flucytosine may be continued uninterrupted for 6-10 weeks
HIV negative: 0.5-0.7 mg/kg/day (plus flucytosine) for 2 weeks
Oropharyngeal candidiasis: I.V.: 0.3 mg/kg/day for 7-14 days (Pappas, 2009)
Osteoarticular candidiasis: I.V.: 0.5-1 mg/kg/day for several weeks, followed by fluconazole for 6-12 months (osteomyelitis) or 6 weeks (septic arthritis)
Penicillium marneffei: I.V.: 0.6 mg/kg/day for 2 weeks
Pneumonia: Cryptococcal (mild-to-moderate): I.V.:
HIV positive: 0.5-1 mg/kg/day
HIV negative: 0.5-0.7 mg/kg/day (plus flucytosine) for 2 weeks
Sporotrichosis: Pulmonary, meningeal, osteoarticular or disseminated: I.V.: Total dose of 1-2 g, then change to oral itraconazole or fluconazole for suppressive therapy
Urinary tract candidiasis (Pappas, 2009):
Fungus balls: I.V.: 0.5-0.7 mg/kg/day with or without flucytosine 25 mg/kg 4 times daily
Pyelonephritis: I.V.: 0.5-0.7 mg/kg/day with or without flucytosine 25 mg/kg 4 times daily for 2 weeks
Symptomatic cystitis: I.V.: 0.3-0.6 mg/kg/day for 1-7 days
Bladder irrigation: Irrigate with 50 mcg/mL solution instilled periodically or continuously for 5-10 days or until cultures are clear for fluconazole-resistant Candida
DOSING: PEDIATRIC — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
(For additional information see "Amphotericin B (conventional): Pediatric drug information")
Test dose: I.V.: Infants and Children: 0.1 mg/kg/dose to a maximum of 1 mg; infuse over 30-60 minutes. Many clinicians believe a test dose is unnecessary.
Susceptible fungal infections: I.V.: Infants and Children: Maintenance dose: 0.25-1 mg/kg/day given once daily; infuse over 2-6 hours. Once therapy has been established, amphotericin B can be administered on an every-other-day basis at 1-1.5 mg/kg/dose; cumulative dose: 1.5-2 g over 6-10 weeks
Note: Duration of therapy varies with nature of infection: Usual duration is 4-12 weeks or cumulative dose of 1-4 g.
Meningitis, coccidioidal or cryptococcal: I.T.: Children: 25-100 mcg every 48-72 hours; increase to 500 mcg as tolerated
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
If renal dysfunction is due to the drug, the daily total can be decreased by 50% or the dose can be given every other day. I.V. therapy may take several months.
Poorly dialyzed; no supplemental dose is necessary when using hemo- or peritoneal dialysis or continuous renal replacement therapy (CRRT).
Administration in dialysate: 1-2 mg/L of peritoneal dialysis fluid either with or without low-dose I.V. amphotericin B (a total dose of 2-10 mg/kg given over 7-14 days). Precipitate may form in ionic dialysate solutions.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as desoxycholate: 50 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — May be infused over 4-6 hours. For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered. Bolus infusion of normal saline immediately preceding, or immediately preceding and following amphotericin B may reduce drug-induced nephrotoxicity. Risk of nephrotoxicity increases with amphotericin B doses >1 mg/kg/day. Infusion of admixtures more concentrated than 0.25 mg/mL should be limited to patients absolutely requiring volume contraction.
COMPATIBILITY
Solution compatibility:
Compatible: Heparin sodium, hydrocortisone, sodium bicarbonate.
Incompatible: Ampicillin, calcium gluconate, carbenicillin, cimetidine, dopamine, gentamicin, lidocaine, potassium chloride, sodium chloride, tetracycline, verapamil.
USE — Treatment of severe systemic and central nervous system infections caused by susceptible fungi such as Candida species, Histoplasma capsulatum, Cryptococcus neoformans, Aspergillus species, Blastomyces dermatitidis, Torulopsis glabrata, and Coccidioides immitis; fungal peritonitis; irrigant for bladder fungal infections; used in fungal infection in patients with bone marrow transplantation, amebic meningoencephalitis, ocular aspergillosis (intraocular injection), candidal cystitis (bladder irrigation), chemoprophylaxis (low-dose I.V.), immunocompromised patients at risk of aspergillosis (intranasal/nebulized), refractory meningitis (intrathecal), coccidioidal arthritis (intra-articular/I.M.).
Low-dose amphotericin B has been administered after bone marrow transplantation to reduce the risk of invasive fungal disease.
ADVERSE REACTIONS SIGNIFICANT
Systemic:
>10%:
Cardiovascular: Hypotension, tachypnea
Central nervous system: Fever, chills, headache (less frequent with I.T.), malaise
Endocrine & metabolic: Hypokalemia, hypomagnesemia
Gastrointestinal: Anorexia, nausea (less frequent with I.T.), vomiting (less frequent with I.T.), diarrhea, heartburn, cramping epigastric pain
Hematologic: Normochromic-normocytic anemia
Local: Pain at injection site with or without phlebitis or thrombophlebitis (incidence may increase with peripheral infusion of admixtures)
Neuromuscular & skeletal: Generalized pain, including muscle and joint pains (less frequent with I.T.)
Renal: Decreased renal function and renal function abnormalities including azotemia, renal tubular acidosis, nephrocalcinosis (>0.1 mg/mL)
1% to 10%:
Cardiovascular: Hypertension, flushing
Central nervous system: Delirium, arachnoiditis, pain along lumbar nerves (especially I.T. therapy)
Genitourinary: Urinary retention
Hematologic: Leukocytosis
Neuromuscular & skeletal: Paresthesia (especially with I.T. therapy)
<1% (Limited to important or life-threatening): Acute liver failure, agranulocytosis, anuria, bone marrow suppression, cardiac arrest, coagulation defects, convulsions, dyspnea, hearing loss, leukopenia, maculopapular rash, renal failure, renal tubular acidosis, thrombocytopenia, vision changes
CONTRAINDICATIONS — Hypersensitivity to amphotericin or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Error prevention: See "Other warnings/precautions" below. Fungal infections: See "Disease-related concerns" below.
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Acute reactions (including fever and chills) may occur 1-3 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses.
Disease-related concerns: Fungal infections: [U.S. Boxed Warning]: Should be used primarily for treatment of progressive, potentially life-threatening fungal infections, not noninvasive forms of infection. Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues: Nephrotoxic drugs: Avoid use with other nephrotoxic drugs; drug-induced renal toxicity usually improves with interrupting therapy, decreasing dosage, or increasing dosing interval.
Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
Other warnings/precautions: Error prevention: [U.S. Boxed warning]: Verify the product name and dosage if dose exceeds 1.5 mg/kg.
DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy
Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Excretion in breast milk unknown/contraindicated
MONITORING PARAMETERS — Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc)
REFERENCE RANGE — Therapeutic: 1-2 mcg/mL (SI: 1-2.2 µmol/L)
CANADIAN BRAND NAMES — Fungizone®
INTERNATIONAL BRAND NAMES — Amphocil (MX); Fungizone (PL); Terix (MX)
MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages (Lyman, 1992).
PHARMACODYNAMICS / KINETICS
Distribution: Minimal amounts enter the aqueous humor, bile, CSF (inflamed or noninflamed meninges), amniotic fluid, pericardial fluid, pleural fluid, and synovial fluid
Protein binding, plasma: 90%
Half-life elimination: Biphasic: Initial: 15-48 hours; Terminal: 15 days
Time to peak: Within 1 hour following a 4- to 6-hour dose
Excretion: Urine (2% to 5% as biologically active form); ~40% eliminated over a 7-day period and may be detected in urine for at least 7 weeks after discontinued उसे.
Safety issues:
Conventional amphotericin formulations (Amphocin®, Fungizone®) may be confused with lipid-based formulations (AmBisome®, Abelcet®, Amphotec®).
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral
DOSING: ADULTS — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Test dose: I.V.: 1 mg infused over 20-30 minutes. Many clinicians believe a test dose is unnecessary.
Susceptible fungal infections: I.V.: Adults: 0.05-1.5 mg/kg/day; 1-1.5 mg/kg over 4-6 hours every other day may be given once therapy is established; aspergillosis, rhinocerebral mucormycosis, often require 1-1.5 mg/kg/day; do not exceed 1.5 mg/kg/day
Aspergillosis, disseminated: I.V.: 0.6-0.7 mg/kg/day for 3-6 months
Bone marrow transplantation (prophylaxis): I.V.: Low-dose amphotericin B 0.1-0.25 mg/kg/day has been administered after bone marrow transplantation to reduce the risk of invasive fungal disease.
Candidemia (neutropenic or non-neutropenic): I.V.: 0.5-1 mg/kg/day until 14 days after last positive blood culture and resolution of signs and symptoms (Pappas, 2009)
Candidiasis, chronic, disseminated: I.V.: 0.5-0.7 mg/kg/day for 3-6 months and resolution of radiologic lesions (Pappas, 2009)
Dematiaceous fungi: I.V.: 0.7 mg/kg/day in combination with an azole
Endocarditis: I.V.: 0.6-1 mg/kg/day (with or without flucytosine) for 6 weeks after valve replacement; Note: If isolates susceptible and/or clearance demonstrated, guidelines recommend step-down to fluconazole; also for long-term suppression therapy if valve replacement is not possible (Pappas, 2009)
Endophthalmitis, fungal:
Intravitreal (unlabeled use): 10 mcg in 0.1 mL (in conjunction with systemic therapy)
I.V.: 0.7-1 mg/kg/day (with or without flucytosine) for at least 4-6 weeks (Pappas, 2009)
Esophageal: I.V.: 0.3-0.7 mg/kg/day for 14-21 days after clinical improvement
Histoplasmosis: Chronic, severe pulmonary or disseminated: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8 mg/kg every other day (or 3 times/week) until total dose of 10-15 mg/kg; may continue itraconazole as suppressive therapy (lifelong for immunocompromised patients)
Meningitis:
Candidal: I.V.: 0.7-1 mg/kg/day (with or without flucytosine) for at least 4 weeks; Note: Liposomal amphotericin favored by IDSA guidelines based on decreased risk of nephrotoxicity and potentially better CNS penetration (Pappas, 2009)
Cryptococcal or Coccidioides: I.T.: Initial: 25-300 mcg every 48-72 hours; increase to 500 mcg to 1 mg as tolerated; maximum total dose: 15 mg has been suggested
Histoplasma: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8 mg/kg every other day (or 3 times/week) for 3 months total duration; follow with fluconazole suppressive therapy for up to 12 months
Meningoencephalitis, cryptococcal: I.V.:
HIV positive: 0.7-1 mg/kg/day (plus flucytosine 100 mg/kg/day) for 2 weeks, then change to oral fluconazole for at least 10 weeks; alternatively, amphotericin and flucytosine may be continued uninterrupted for 6-10 weeks
HIV negative: 0.5-0.7 mg/kg/day (plus flucytosine) for 2 weeks
Oropharyngeal candidiasis: I.V.: 0.3 mg/kg/day for 7-14 days (Pappas, 2009)
Osteoarticular candidiasis: I.V.: 0.5-1 mg/kg/day for several weeks, followed by fluconazole for 6-12 months (osteomyelitis) or 6 weeks (septic arthritis)
Penicillium marneffei: I.V.: 0.6 mg/kg/day for 2 weeks
Pneumonia: Cryptococcal (mild-to-moderate): I.V.:
HIV positive: 0.5-1 mg/kg/day
HIV negative: 0.5-0.7 mg/kg/day (plus flucytosine) for 2 weeks
Sporotrichosis: Pulmonary, meningeal, osteoarticular or disseminated: I.V.: Total dose of 1-2 g, then change to oral itraconazole or fluconazole for suppressive therapy
Urinary tract candidiasis (Pappas, 2009):
Fungus balls: I.V.: 0.5-0.7 mg/kg/day with or without flucytosine 25 mg/kg 4 times daily
Pyelonephritis: I.V.: 0.5-0.7 mg/kg/day with or without flucytosine 25 mg/kg 4 times daily for 2 weeks
Symptomatic cystitis: I.V.: 0.3-0.6 mg/kg/day for 1-7 days
Bladder irrigation: Irrigate with 50 mcg/mL solution instilled periodically or continuously for 5-10 days or until cultures are clear for fluconazole-resistant Candida
DOSING: PEDIATRIC — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
(For additional information see "Amphotericin B (conventional): Pediatric drug information")
Test dose: I.V.: Infants and Children: 0.1 mg/kg/dose to a maximum of 1 mg; infuse over 30-60 minutes. Many clinicians believe a test dose is unnecessary.
Susceptible fungal infections: I.V.: Infants and Children: Maintenance dose: 0.25-1 mg/kg/day given once daily; infuse over 2-6 hours. Once therapy has been established, amphotericin B can be administered on an every-other-day basis at 1-1.5 mg/kg/dose; cumulative dose: 1.5-2 g over 6-10 weeks
Note: Duration of therapy varies with nature of infection: Usual duration is 4-12 weeks or cumulative dose of 1-4 g.
Meningitis, coccidioidal or cryptococcal: I.T.: Children: 25-100 mcg every 48-72 hours; increase to 500 mcg as tolerated
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
If renal dysfunction is due to the drug, the daily total can be decreased by 50% or the dose can be given every other day. I.V. therapy may take several months.
Poorly dialyzed; no supplemental dose is necessary when using hemo- or peritoneal dialysis or continuous renal replacement therapy (CRRT).
Administration in dialysate: 1-2 mg/L of peritoneal dialysis fluid either with or without low-dose I.V. amphotericin B (a total dose of 2-10 mg/kg given over 7-14 days). Precipitate may form in ionic dialysate solutions.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as desoxycholate: 50 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — May be infused over 4-6 hours. For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered. Bolus infusion of normal saline immediately preceding, or immediately preceding and following amphotericin B may reduce drug-induced nephrotoxicity. Risk of nephrotoxicity increases with amphotericin B doses >1 mg/kg/day. Infusion of admixtures more concentrated than 0.25 mg/mL should be limited to patients absolutely requiring volume contraction.
COMPATIBILITY
Solution compatibility:
Compatible: Heparin sodium, hydrocortisone, sodium bicarbonate.
Incompatible: Ampicillin, calcium gluconate, carbenicillin, cimetidine, dopamine, gentamicin, lidocaine, potassium chloride, sodium chloride, tetracycline, verapamil.
USE — Treatment of severe systemic and central nervous system infections caused by susceptible fungi such as Candida species, Histoplasma capsulatum, Cryptococcus neoformans, Aspergillus species, Blastomyces dermatitidis, Torulopsis glabrata, and Coccidioides immitis; fungal peritonitis; irrigant for bladder fungal infections; used in fungal infection in patients with bone marrow transplantation, amebic meningoencephalitis, ocular aspergillosis (intraocular injection), candidal cystitis (bladder irrigation), chemoprophylaxis (low-dose I.V.), immunocompromised patients at risk of aspergillosis (intranasal/nebulized), refractory meningitis (intrathecal), coccidioidal arthritis (intra-articular/I.M.).
Low-dose amphotericin B has been administered after bone marrow transplantation to reduce the risk of invasive fungal disease.
ADVERSE REACTIONS SIGNIFICANT
Systemic:
>10%:
Cardiovascular: Hypotension, tachypnea
Central nervous system: Fever, chills, headache (less frequent with I.T.), malaise
Endocrine & metabolic: Hypokalemia, hypomagnesemia
Gastrointestinal: Anorexia, nausea (less frequent with I.T.), vomiting (less frequent with I.T.), diarrhea, heartburn, cramping epigastric pain
Hematologic: Normochromic-normocytic anemia
Local: Pain at injection site with or without phlebitis or thrombophlebitis (incidence may increase with peripheral infusion of admixtures)
Neuromuscular & skeletal: Generalized pain, including muscle and joint pains (less frequent with I.T.)
Renal: Decreased renal function and renal function abnormalities including azotemia, renal tubular acidosis, nephrocalcinosis (>0.1 mg/mL)
1% to 10%:
Cardiovascular: Hypertension, flushing
Central nervous system: Delirium, arachnoiditis, pain along lumbar nerves (especially I.T. therapy)
Genitourinary: Urinary retention
Hematologic: Leukocytosis
Neuromuscular & skeletal: Paresthesia (especially with I.T. therapy)
<1% (Limited to important or life-threatening): Acute liver failure, agranulocytosis, anuria, bone marrow suppression, cardiac arrest, coagulation defects, convulsions, dyspnea, hearing loss, leukopenia, maculopapular rash, renal failure, renal tubular acidosis, thrombocytopenia, vision changes
CONTRAINDICATIONS — Hypersensitivity to amphotericin or any component of the formulation
WARNINGS / PRECAUTIONS
Boxed warnings: Error prevention: See "Other warnings/precautions" below. Fungal infections: See "Disease-related concerns" below.
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Acute reactions (including fever and chills) may occur 1-3 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses.
Disease-related concerns: Fungal infections: [U.S. Boxed Warning]: Should be used primarily for treatment of progressive, potentially life-threatening fungal infections, not noninvasive forms of infection. Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues: Nephrotoxic drugs: Avoid use with other nephrotoxic drugs; drug-induced renal toxicity usually improves with interrupting therapy, decreasing dosage, or increasing dosing interval.
Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
Other warnings/precautions: Error prevention: [U.S. Boxed warning]: Verify the product name and dosage if dose exceeds 1.5 mg/kg.
DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy
Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Excretion in breast milk unknown/contraindicated
MONITORING PARAMETERS — Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc)
REFERENCE RANGE — Therapeutic: 1-2 mcg/mL (SI: 1-2.2 µmol/L)
CANADIAN BRAND NAMES — Fungizone®
INTERNATIONAL BRAND NAMES — Amphocil (MX); Fungizone (PL); Terix (MX)
MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages (Lyman, 1992).
PHARMACODYNAMICS / KINETICS
Distribution: Minimal amounts enter the aqueous humor, bile, CSF (inflamed or noninflamed meninges), amniotic fluid, pericardial fluid, pleural fluid, and synovial fluid
Protein binding, plasma: 90%
Half-life elimination: Biphasic: Initial: 15-48 hours; Terminal: 15 days
Time to peak: Within 1 hour following a 4- to 6-hour dose
Excretion: Urine (2% to 5% as biologically active form); ~40% eliminated over a 7-day period and may be detected in urine for at least 7 weeks after discontinued उसे.
Amoxicillin and clavulanate potassium
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Augmentin® may be confused with Azulfidine®
U.S. BRAND NAMES — Amoclan; Augmentin ES-600®; Augmentin XR®; Augmentin®
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS — Note: Dose is based on the amoxicillin component; see "Augmentin® Product-Specific Considerations" table.
Susceptible infections: Children >40 kg and Adults: Oral: 250-500 mg every 8 hours or 875 mg every 12 hours
Augmentin® Product-Specific Considerations
125 mg: Chewable tablet: q8h dosing Suspension:
" q8h dosing
" For adults having difficulty swallowing tablets, 125 mg/5 mL suspension may be substituted for 500 mg tablet.
200 mg: Chewable tablet:
" q12h dosing
" Contains phenylalanine Suspension:
" q12h dosing
" For adults having difficulty swallowing tablets, 200 mg/5 mL suspension may be substituted for 875 mg tablet.
250 mg: Chewable tablet:
" q8h dosing
" Contains phenylalanine
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid. Suspension:
" q8h dosing
" For adults having difficulty swallowing tablets, 250 mg/5 mL suspension may be substituted for 500 mg tablet. Tablet:
" q8h dosing
" Not for use in patients <40 kg
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid.
400 mg: Chewable tablet:
" q12h dosing
" Contains phenylalanine Suspension:
" q12h dosing
" For adults having difficulty swallowing tablets, 400 mg/5 mL suspension may be substituted for 875 mg tablet.
500 mg: Tablet: q8h or q12h dosing
600 mg: Suspension:
" q12h dosing
" Not for use in adults or children ≥ 40 kg
" 600 mg/5 mL suspension is not equivalent to or interchangeable with 200 mg/5 mL or 400 mg/5 mL due to differences in clavulanic acid.
875 mg: Tablet:
" q12h dosing
" Not for use in Clcr <30 mL/minute
1000 mg: Extended release tablet:
" q12h dosing
" Not for use in children <16 years of age
" Not interchangeable with two 500 mg tablets
" Not for use if Clcr <30 mL/minute or hemodialysis
Acute bacterial sinusitis: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 10 days
Bite wounds (animal/human): Oral: 875 mg every 12 hours or 500 mg every 8 hours
Chronic obstructive pulmonary disease: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Diabetic foot: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-14 days
Diverticulitis, perirectal abscess: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days
Erysipelas: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Febrile neutropenia: Oral: 875 mg every 12 hours
Pneumonia:
Aspiration: Oral: 875 mg every 12 hours
Community-acquired: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days
Pyelonephritis (acute, uncomplicated): Oral: 875 mg every 12 hours or 500 mg every 8 hours
Skin abscess: Oral: 875 mg every 12 hours
DOSING: PEDIATRIC — Note: Dose is based on the amoxicillin component; see "Augmentin® Product-Specific Considerations" table.
(For additional information see "Amoxicillin and clavulanate potassium: Pediatric drug information")
Susceptible infections: Infants <3 months: Oral: 30 mg/kg/day divided every 12 hours using the 125 mg/5 mL suspension
Lower respiratory tract infections, severe infections, sinusitis: Children ≥ 3 months and <40 kg: Oral: 45 mg/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours
Mild-to-moderate infections: Children ≥ 3 months and <40 kg: Oral: 25 mg/kg/day divided every 12 hours or 20 mg/kg/day divided every 8 hours
Otitis media (Augmentin ES-600®): Children ≥ 3 months and <40 kg: Oral: 90 mg/kg/day divided every 12 hours for 10 days in children with severe illness and when coverage for ß-lactamase positive H. influenzae and M. catarrhalis is needed.
Children >40 kg: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Clcr <30 mL/minute: Do not use 875 mg tablet or extended release tablets.
Clcr 10-30 mL/minute: 250-500 mg every 12 hours
Clcr <10 mL/minute: 250-500 every 24 hours
Hemodialysis: Moderately dialyzable (20% to 50%)
250-500 mg every 24 hours; administer dose during and after dialysis. Do not use extended release tablets.
Peritoneal dialysis: Moderately dialyzable (20% to 50%)
Amoxicillin: Administer 250 mg every 12 hours
Clavulanic acid: Dose for Clcr <10 mL/minute
Continuous arteriovenous or venovenous hemofiltration effects:
Amoxicillin: ~50 mg of amoxicillin/L of filtrate is removed
Clavulanic acid: Dose for Clcr <10 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL)
Amoclan:
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.14 mEq/5 mL; fruit flavor]
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.29 mEq/5 mL; fruit flavor]
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL) [contains phenylalanine 7 mg/5 mL, potassium 0.248 mEq/5 mL; orange flavor]
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.16 mEq/5 mL; banana flavor]
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.14 mEq/5 mL; orange flavor] [DSC]
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.32 mEq/5 mL; orange flavor]
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.29 mEq/5 mL; orange flavor] [DSC]
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.23 mEq/5 mL; strawberry cream flavor]
Tablet: 250: Amoxicillin 250 mg and clavulanate potassium 125 mg; 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
500: Amoxicillin 500 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
875: Amoxicillin 875 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg [contains phenylalanine]
Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg [contains potassium 12.6 mg (0.32 mEq) and sodium 29.3 mg (1.27 mEq) per tablet; packaged in either a 7-day or 10-day package]
DOSAGE FORMS: CONCISE
Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Amoclan:
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Tablet: 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg
500: Amoxicillin 500 mg and clavulanate potassium 125 mg
875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg
Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes extended release
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Administer with food to decrease stomach upset; shake suspension well before use. Extended release tablets should be administered with food.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
USE — Treatment of otitis media, sinusitis, and infections caused by susceptible organisms involving the lower respiratory tract, skin and skin structure, and urinary tract; spectrum same as amoxicillin with additional coverage of beta-lactamase producing B. catarrhalis, H. influenzae, N. gonorrhoeae, and S. aureus (not MRSA). The expanded coverage of this combination makes it a useful alternative when amoxicillin resistance is present and patients cannot tolerate alternative treatments.
ADVERSE REACTIONS SIGNIFICANT
>10%: Gastrointestinal: Diarrhea (3% to 34%; incidence varies upon dose and regimen used)
1% to 10%:
Dermatologic: Diaper rash, skin rash, urticaria
Gastrointestinal: Abdominal discomfort, loose stools, nausea, vomiting
Genitourinary: Vaginitis, vaginal mycosis
Miscellaneous: Moniliasis
<1% (Limited to important or life-threatening): Alkaline phosphatase increased, cholestatic jaundice, flatulence, headache, hepatic dysfunction, hepatitis, liver function tests increased, prothrombin time increased, thrombocytosis, vasculitis (hypersensitivity)
Additional adverse reactions seen with ampicillin-class antibiotics: Agitation, agranulocytosis, alkaline phosphatase increased, anaphylaxis, anemia, angioedema, anxiety, behavioral changes, bilirubin increased, black "hairy" tongue, confusion, convulsions, crystalluria, dizziness, enterocolitis, eosinophilia, erythema multiforme, exanthematous pustulosis, exfoliative dermatitis, gastritis, glossitis, hematuria, hemolytic anemia, hemorrhagic colitis, indigestion, insomnia, hyperactivity, interstitial nephritis, leukopenia, mucocutaneous candidiasis, pruritus, pseudomembranous colitis, serum sickness-like reaction, Stevens-Johnson syndrome, stomatitis, transaminases increased, thrombocytopenia, thrombocytopenic purpura, tooth discoloration, toxic epidermal necrolysis
CONTRAINDICATIONS — Hypersensitivity to amoxicillin, clavulanic acid, penicillin, or any component of the formulation; history of cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanate potassium therapy; Augmentin XR™ : severe renal impairment (Clcr <30 mL/minute) and hemodialysis patients
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Low incidence of cross-allergy with cephalosporins exists. Diarrhea: Incidence of diarrhea is higher than with amoxicillin alone. Hepatic effects: Although rare, hepatic dysfunction is more common in elderly and/or males, and occurs more frequently with prolonged treatment, and may occur after therapy is complete. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hepatic impairment: Use with caution in patients with hepatic impairment. Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Dosage form specific issues: Clavulanic acid content: Due to differing content of clavulanic acid, not all formulations are interchangeable. Phenylalanine: Some products contain phenylalanine.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, amoxicillin/clavulanate is classified as pregnancy category B. Both amoxicillin and clavulanic acid cross the placenta. There is no documented increased risk of teratogenic effects caused by amoxicillin/clavulanate. A potential increased risk of necrotizing enterocolitis in the newborn has been noted after maternal use of amoxicillin/clavulanate for preterm labor or premature prolonged rupture of membranes. When used during pregnancy, pharmacokinetic changes have been observed with amoxicillin alone (refer to the Amoxicillin monograph for details).
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Amoxicillin is found in breast milk. The manufacturer recommends that caution be used if administered to breast-feeding women. The use of amoxicillin/clavulanate may be safe while breast-feeding; however, the risk of adverse events in the infant may be increased when compared to the use of amoxicillin alone. The risk of adverse events may be related to maternal dose. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant.
DIETARY CONSIDERATIONS — May be taken with meals or on an empty stomach; take with meals to increase absorption and decrease GI intolerance; may mix with milk, formula, or juice. Extended release tablets should be taken with food. Some products contain phenylalanine. If you have phenylketonuria or PKU, avoid use. All dosage forms contain potassium.
PRICING — (data from drugstore.com)
Chewable (Amoxicillin-Pot Clavulanate)
400-57 mg (20): $63.79
Suspension (reconstituted) (Amoxicillin-Pot Clavulanate)
600-42.9 mg/5 mL (75): $35.99
Tablet, 12-hour (Augmentin XR)
1000-62.5 mg (28): $116.70
Tablets (Amoxicillin-Pot Clavulanate)
250-125 mg (30): $116.54
500-125 mg (20): $45.99
875-125 mg (20): $31.99
Tablets (Augmentin)
250-125 mg (30): $118.99
500-125 mg (30): $166.71
875-125 mg (20): $145.99
MONITORING PARAMETERS — Assess patient at beginning and throughout therapy for infection; with prolonged therapy, monitor renal, hepatic, and hematologic function periodically; monitor for signs of anaphylaxis during first dose
CANADIAN BRAND NAMES — Alti-Amoxi-Clav; Apo-Amoxi-Clav®; Augmentin®; Clavulin®; Novo-Clavamoxin; ratio-Aclavulanate
INTERNATIONAL BRAND NAMES — Acarbixin (MX); Aclam (ID); Ambilan (PE); AMK (TH); Amobay Cl (MX); Amocla (KP); Amocla Duo (KP); Amoclan (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amoclav (DE); Amoksiclav (TH); Amoksiklav (CL, PL); Amolanic (KP); Amolanic Duo (KP); Amoxa (KP); Amoxi Plus (PY); Amoxiclav (MX); Amoxiclav-BID (MX); Amoxiclav-Teva (IL); Amoxsiklav Forte (TH); Amoxxlin (KP); Amoxyclav (IL); Augamox (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); AugMaxcil (ZA); Augmentan (DE); Augmentin (AE, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, OM, PA, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TH, TN, TR, TT, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Augmentine (ES); Augmex (PH); Augpen (TH); Augurcin (PH); Bactiv (PH); Bactoclav (PH); Bioclavid (AE, BH, CY, DE, DK, EG, IL, IQ, IR, JO, KW, LB, LY, OM, PH, QA, SA, SE, SY, YE); Bioclavid Forte (PH); Cavumox (MY, TH); Cax (PH); Clacillin Duo Dry Syrup (KP); Clamax (KP); Clamentin (ZA); Clamohexal (AU); Clamohexal Duo (AU); Clamovid (HK, MY, SG); Clamoxin (MX); Clamoxyl (AU); Clamoxyl Duo 400 (AU); Clamoxyl DuoForte (AU); Clavamox (DE, ID, IN); Clavant (MX); Clavar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Claventin (IL); Clavinex (CN, EC); Clavipen (MX); Clavmex (PH); Clavodar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Clavoxil (BR); Clavoxine (EC); Clavucyd (MX); Clavulin (BF, BJ, CI, CO, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, MX, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Clavulin Duo Forte (AU); Clavulox Duo (AR, PY); Clavumox (DE, PE, ZA); Clavuser (MX); Cramon Duo (KP); Curam (AU, CO, CR, DO, GT, HK, MY, NI, PA, PE, PL, SG, SV, TH, TW); Danoclav (ID); Darzitil Plus (AR); E-Moxclav (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Enhancin (SG); Exten (PH); Fleming (HK); Forcid (PL); Fugentin (SG); Fullicilina Plus (AR); Gimaclav (MX); Hibiotic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Klamonex (KP); Klavic (PH); Klavocin (PL); Kmoxilin (KP); Lansiclav (ID); Moxiclav (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Moxicle (KP, TH); Moxlin (MX); Natravox (PH); Novamox (BR); Nufaclav (ID); Penhance (PH); Quali-Mentin (HK); Ramoclav (PL); Ranclav (TH, ZA); Riclasip (MX); Servamox (MX); Sinufin (MX); Spektramox (SE); Sullivan (PH); Suplentin (PH); Synermox (NZ); Taromentin (PL); Velamox CL (PE); Vestaclav (MY); Viaclav (ID); Vulamox (CO, ID)
MECHANISM OF ACTION — Clavulanic acid binds and inhibits beta-lactamases that inactivate amoxicillin resulting in amoxicillin having an expanded spectrum of activity. Amoxicillin inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS — Amoxicillin pharmacokinetics are not affected by clavulanic acid.
Amoxicillin: See Amoxicillin monograph.
Clavulanic acid:
Protein binding: ~25%
Metabolism: Hepatic
Half-life elimination: 1 hour
Time to peak: 1 hour
Excretion: Urine (30% to 40% as unchanged drug)
PATIENT INFORMATION — Take entire course of medication. Take extended release tablets with food. Report diarrhea promptly. Females should report onset of symptoms of candidal vaginitis
Sound-alike/look-alike issues:
Augmentin® may be confused with Azulfidine®
U.S. BRAND NAMES — Amoclan; Augmentin ES-600®; Augmentin XR®; Augmentin®
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS — Note: Dose is based on the amoxicillin component; see "Augmentin® Product-Specific Considerations" table.
Susceptible infections: Children >40 kg and Adults: Oral: 250-500 mg every 8 hours or 875 mg every 12 hours
Augmentin® Product-Specific Considerations
125 mg: Chewable tablet: q8h dosing Suspension:
" q8h dosing
" For adults having difficulty swallowing tablets, 125 mg/5 mL suspension may be substituted for 500 mg tablet.
200 mg: Chewable tablet:
" q12h dosing
" Contains phenylalanine Suspension:
" q12h dosing
" For adults having difficulty swallowing tablets, 200 mg/5 mL suspension may be substituted for 875 mg tablet.
250 mg: Chewable tablet:
" q8h dosing
" Contains phenylalanine
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid. Suspension:
" q8h dosing
" For adults having difficulty swallowing tablets, 250 mg/5 mL suspension may be substituted for 500 mg tablet. Tablet:
" q8h dosing
" Not for use in patients <40 kg
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid.
400 mg: Chewable tablet:
" q12h dosing
" Contains phenylalanine Suspension:
" q12h dosing
" For adults having difficulty swallowing tablets, 400 mg/5 mL suspension may be substituted for 875 mg tablet.
500 mg: Tablet: q8h or q12h dosing
600 mg: Suspension:
" q12h dosing
" Not for use in adults or children ≥ 40 kg
" 600 mg/5 mL suspension is not equivalent to or interchangeable with 200 mg/5 mL or 400 mg/5 mL due to differences in clavulanic acid.
875 mg: Tablet:
" q12h dosing
" Not for use in Clcr <30 mL/minute
1000 mg: Extended release tablet:
" q12h dosing
" Not for use in children <16 years of age
" Not interchangeable with two 500 mg tablets
" Not for use if Clcr <30 mL/minute or hemodialysis
Acute bacterial sinusitis: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 10 days
Bite wounds (animal/human): Oral: 875 mg every 12 hours or 500 mg every 8 hours
Chronic obstructive pulmonary disease: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Diabetic foot: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-14 days
Diverticulitis, perirectal abscess: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days
Erysipelas: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Febrile neutropenia: Oral: 875 mg every 12 hours
Pneumonia:
Aspiration: Oral: 875 mg every 12 hours
Community-acquired: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days
Pyelonephritis (acute, uncomplicated): Oral: 875 mg every 12 hours or 500 mg every 8 hours
Skin abscess: Oral: 875 mg every 12 hours
DOSING: PEDIATRIC — Note: Dose is based on the amoxicillin component; see "Augmentin® Product-Specific Considerations" table.
(For additional information see "Amoxicillin and clavulanate potassium: Pediatric drug information")
Susceptible infections: Infants <3 months: Oral: 30 mg/kg/day divided every 12 hours using the 125 mg/5 mL suspension
Lower respiratory tract infections, severe infections, sinusitis: Children ≥ 3 months and <40 kg: Oral: 45 mg/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours
Mild-to-moderate infections: Children ≥ 3 months and <40 kg: Oral: 25 mg/kg/day divided every 12 hours or 20 mg/kg/day divided every 8 hours
Otitis media (Augmentin ES-600®): Children ≥ 3 months and <40 kg: Oral: 90 mg/kg/day divided every 12 hours for 10 days in children with severe illness and when coverage for ß-lactamase positive H. influenzae and M. catarrhalis is needed.
Children >40 kg: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Clcr <30 mL/minute: Do not use 875 mg tablet or extended release tablets.
Clcr 10-30 mL/minute: 250-500 mg every 12 hours
Clcr <10 mL/minute: 250-500 every 24 hours
Hemodialysis: Moderately dialyzable (20% to 50%)
250-500 mg every 24 hours; administer dose during and after dialysis. Do not use extended release tablets.
Peritoneal dialysis: Moderately dialyzable (20% to 50%)
Amoxicillin: Administer 250 mg every 12 hours
Clavulanic acid: Dose for Clcr <10 mL/minute
Continuous arteriovenous or venovenous hemofiltration effects:
Amoxicillin: ~50 mg of amoxicillin/L of filtrate is removed
Clavulanic acid: Dose for Clcr <10 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL)
Amoclan:
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.14 mEq/5 mL; fruit flavor]
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.29 mEq/5 mL; fruit flavor]
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL) [contains phenylalanine 7 mg/5 mL, potassium 0.248 mEq/5 mL; orange flavor]
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.16 mEq/5 mL; banana flavor]
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.14 mEq/5 mL; orange flavor] [DSC]
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.32 mEq/5 mL; orange flavor]
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.29 mEq/5 mL; orange flavor] [DSC]
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.23 mEq/5 mL; strawberry cream flavor]
Tablet: 250: Amoxicillin 250 mg and clavulanate potassium 125 mg; 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
500: Amoxicillin 500 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
875: Amoxicillin 875 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg [contains phenylalanine]
Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg [contains potassium 12.6 mg (0.32 mEq) and sodium 29.3 mg (1.27 mEq) per tablet; packaged in either a 7-day or 10-day package]
DOSAGE FORMS: CONCISE
Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Amoclan:
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Tablet: 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg
500: Amoxicillin 500 mg and clavulanate potassium 125 mg
875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg
Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes extended release
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Administer with food to decrease stomach upset; shake suspension well before use. Extended release tablets should be administered with food.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
USE — Treatment of otitis media, sinusitis, and infections caused by susceptible organisms involving the lower respiratory tract, skin and skin structure, and urinary tract; spectrum same as amoxicillin with additional coverage of beta-lactamase producing B. catarrhalis, H. influenzae, N. gonorrhoeae, and S. aureus (not MRSA). The expanded coverage of this combination makes it a useful alternative when amoxicillin resistance is present and patients cannot tolerate alternative treatments.
ADVERSE REACTIONS SIGNIFICANT
>10%: Gastrointestinal: Diarrhea (3% to 34%; incidence varies upon dose and regimen used)
1% to 10%:
Dermatologic: Diaper rash, skin rash, urticaria
Gastrointestinal: Abdominal discomfort, loose stools, nausea, vomiting
Genitourinary: Vaginitis, vaginal mycosis
Miscellaneous: Moniliasis
<1% (Limited to important or life-threatening): Alkaline phosphatase increased, cholestatic jaundice, flatulence, headache, hepatic dysfunction, hepatitis, liver function tests increased, prothrombin time increased, thrombocytosis, vasculitis (hypersensitivity)
Additional adverse reactions seen with ampicillin-class antibiotics: Agitation, agranulocytosis, alkaline phosphatase increased, anaphylaxis, anemia, angioedema, anxiety, behavioral changes, bilirubin increased, black "hairy" tongue, confusion, convulsions, crystalluria, dizziness, enterocolitis, eosinophilia, erythema multiforme, exanthematous pustulosis, exfoliative dermatitis, gastritis, glossitis, hematuria, hemolytic anemia, hemorrhagic colitis, indigestion, insomnia, hyperactivity, interstitial nephritis, leukopenia, mucocutaneous candidiasis, pruritus, pseudomembranous colitis, serum sickness-like reaction, Stevens-Johnson syndrome, stomatitis, transaminases increased, thrombocytopenia, thrombocytopenic purpura, tooth discoloration, toxic epidermal necrolysis
CONTRAINDICATIONS — Hypersensitivity to amoxicillin, clavulanic acid, penicillin, or any component of the formulation; history of cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanate potassium therapy; Augmentin XR™ : severe renal impairment (Clcr <30 mL/minute) and hemodialysis patients
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Low incidence of cross-allergy with cephalosporins exists. Diarrhea: Incidence of diarrhea is higher than with amoxicillin alone. Hepatic effects: Although rare, hepatic dysfunction is more common in elderly and/or males, and occurs more frequently with prolonged treatment, and may occur after therapy is complete. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hepatic impairment: Use with caution in patients with hepatic impairment. Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Dosage form specific issues: Clavulanic acid content: Due to differing content of clavulanic acid, not all formulations are interchangeable. Phenylalanine: Some products contain phenylalanine.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, amoxicillin/clavulanate is classified as pregnancy category B. Both amoxicillin and clavulanic acid cross the placenta. There is no documented increased risk of teratogenic effects caused by amoxicillin/clavulanate. A potential increased risk of necrotizing enterocolitis in the newborn has been noted after maternal use of amoxicillin/clavulanate for preterm labor or premature prolonged rupture of membranes. When used during pregnancy, pharmacokinetic changes have been observed with amoxicillin alone (refer to the Amoxicillin monograph for details).
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Amoxicillin is found in breast milk. The manufacturer recommends that caution be used if administered to breast-feeding women. The use of amoxicillin/clavulanate may be safe while breast-feeding; however, the risk of adverse events in the infant may be increased when compared to the use of amoxicillin alone. The risk of adverse events may be related to maternal dose. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant.
DIETARY CONSIDERATIONS — May be taken with meals or on an empty stomach; take with meals to increase absorption and decrease GI intolerance; may mix with milk, formula, or juice. Extended release tablets should be taken with food. Some products contain phenylalanine. If you have phenylketonuria or PKU, avoid use. All dosage forms contain potassium.
PRICING — (data from drugstore.com)
Chewable (Amoxicillin-Pot Clavulanate)
400-57 mg (20): $63.79
Suspension (reconstituted) (Amoxicillin-Pot Clavulanate)
600-42.9 mg/5 mL (75): $35.99
Tablet, 12-hour (Augmentin XR)
1000-62.5 mg (28): $116.70
Tablets (Amoxicillin-Pot Clavulanate)
250-125 mg (30): $116.54
500-125 mg (20): $45.99
875-125 mg (20): $31.99
Tablets (Augmentin)
250-125 mg (30): $118.99
500-125 mg (30): $166.71
875-125 mg (20): $145.99
MONITORING PARAMETERS — Assess patient at beginning and throughout therapy for infection; with prolonged therapy, monitor renal, hepatic, and hematologic function periodically; monitor for signs of anaphylaxis during first dose
CANADIAN BRAND NAMES — Alti-Amoxi-Clav; Apo-Amoxi-Clav®; Augmentin®; Clavulin®; Novo-Clavamoxin; ratio-Aclavulanate
INTERNATIONAL BRAND NAMES — Acarbixin (MX); Aclam (ID); Ambilan (PE); AMK (TH); Amobay Cl (MX); Amocla (KP); Amocla Duo (KP); Amoclan (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amoclav (DE); Amoksiclav (TH); Amoksiklav (CL, PL); Amolanic (KP); Amolanic Duo (KP); Amoxa (KP); Amoxi Plus (PY); Amoxiclav (MX); Amoxiclav-BID (MX); Amoxiclav-Teva (IL); Amoxsiklav Forte (TH); Amoxxlin (KP); Amoxyclav (IL); Augamox (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); AugMaxcil (ZA); Augmentan (DE); Augmentin (AE, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, OM, PA, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TH, TN, TR, TT, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Augmentine (ES); Augmex (PH); Augpen (TH); Augurcin (PH); Bactiv (PH); Bactoclav (PH); Bioclavid (AE, BH, CY, DE, DK, EG, IL, IQ, IR, JO, KW, LB, LY, OM, PH, QA, SA, SE, SY, YE); Bioclavid Forte (PH); Cavumox (MY, TH); Cax (PH); Clacillin Duo Dry Syrup (KP); Clamax (KP); Clamentin (ZA); Clamohexal (AU); Clamohexal Duo (AU); Clamovid (HK, MY, SG); Clamoxin (MX); Clamoxyl (AU); Clamoxyl Duo 400 (AU); Clamoxyl DuoForte (AU); Clavamox (DE, ID, IN); Clavant (MX); Clavar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Claventin (IL); Clavinex (CN, EC); Clavipen (MX); Clavmex (PH); Clavodar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Clavoxil (BR); Clavoxine (EC); Clavucyd (MX); Clavulin (BF, BJ, CI, CO, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, MX, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Clavulin Duo Forte (AU); Clavulox Duo (AR, PY); Clavumox (DE, PE, ZA); Clavuser (MX); Cramon Duo (KP); Curam (AU, CO, CR, DO, GT, HK, MY, NI, PA, PE, PL, SG, SV, TH, TW); Danoclav (ID); Darzitil Plus (AR); E-Moxclav (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Enhancin (SG); Exten (PH); Fleming (HK); Forcid (PL); Fugentin (SG); Fullicilina Plus (AR); Gimaclav (MX); Hibiotic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Klamonex (KP); Klavic (PH); Klavocin (PL); Kmoxilin (KP); Lansiclav (ID); Moxiclav (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Moxicle (KP, TH); Moxlin (MX); Natravox (PH); Novamox (BR); Nufaclav (ID); Penhance (PH); Quali-Mentin (HK); Ramoclav (PL); Ranclav (TH, ZA); Riclasip (MX); Servamox (MX); Sinufin (MX); Spektramox (SE); Sullivan (PH); Suplentin (PH); Synermox (NZ); Taromentin (PL); Velamox CL (PE); Vestaclav (MY); Viaclav (ID); Vulamox (CO, ID)
MECHANISM OF ACTION — Clavulanic acid binds and inhibits beta-lactamases that inactivate amoxicillin resulting in amoxicillin having an expanded spectrum of activity. Amoxicillin inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS — Amoxicillin pharmacokinetics are not affected by clavulanic acid.
Amoxicillin: See Amoxicillin monograph.
Clavulanic acid:
Protein binding: ~25%
Metabolism: Hepatic
Half-life elimination: 1 hour
Time to peak: 1 hour
Excretion: Urine (30% to 40% as unchanged drug)
PATIENT INFORMATION — Take entire course of medication. Take extended release tablets with food. Report diarrhea promptly. Females should report onset of symptoms of candidal vaginitis
Amoxicillin and clavulanate potassium
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Augmentin® may be confused with Azulfidine®
U.S. BRAND NAMES — Amoclan; Augmentin ES-600®; Augmentin XR®; Augmentin®
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS — Note: Dose is based on the amoxicillin component; see "Augmentin® Product-Specific Considerations" table.
Susceptible infections: Children >40 kg and Adults: Oral: 250-500 mg every 8 hours or 875 mg every 12 hours
Augmentin® Product-Specific Considerations
125 mg: Chewable tablet: q8h dosing Suspension:
" q8h dosing
" For adults having difficulty swallowing tablets, 125 mg/5 mL suspension may be substituted for 500 mg tablet.
200 mg: Chewable tablet:
" q12h dosing
" Contains phenylalanine Suspension:
" q12h dosing
" For adults having difficulty swallowing tablets, 200 mg/5 mL suspension may be substituted for 875 mg tablet.
250 mg: Chewable tablet:
" q8h dosing
" Contains phenylalanine
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid. Suspension:
" q8h dosing
" For adults having difficulty swallowing tablets, 250 mg/5 mL suspension may be substituted for 500 mg tablet. Tablet:
" q8h dosing
" Not for use in patients <40 kg
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid.
400 mg: Chewable tablet:
" q12h dosing
" Contains phenylalanine Suspension:
" q12h dosing
" For adults having difficulty swallowing tablets, 400 mg/5 mL suspension may be substituted for 875 mg tablet.
500 mg: Tablet: q8h or q12h dosing
600 mg: Suspension:
" q12h dosing
" Not for use in adults or children ≥ 40 kg
" 600 mg/5 mL suspension is not equivalent to or interchangeable with 200 mg/5 mL or 400 mg/5 mL due to differences in clavulanic acid.
875 mg: Tablet:
" q12h dosing
" Not for use in Clcr <30 mL/minute
1000 mg: Extended release tablet:
" q12h dosing
" Not for use in children <16 years of age
" Not interchangeable with two 500 mg tablets
" Not for use if Clcr <30 mL/minute or hemodialysis
Acute bacterial sinusitis: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 10 days
Bite wounds (animal/human): Oral: 875 mg every 12 hours or 500 mg every 8 hours
Chronic obstructive pulmonary disease: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Diabetic foot: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-14 days
Diverticulitis, perirectal abscess: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days
Erysipelas: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Febrile neutropenia: Oral: 875 mg every 12 hours
Pneumonia:
Aspiration: Oral: 875 mg every 12 hours
Community-acquired: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days
Pyelonephritis (acute, uncomplicated): Oral: 875 mg every 12 hours or 500 mg every 8 hours
Skin abscess: Oral: 875 mg every 12 hours
DOSING: PEDIATRIC — Note: Dose is based on the amoxicillin component; see "Augmentin® Product-Specific Considerations" table.
(For additional information see "Amoxicillin and clavulanate potassium: Pediatric drug information")
Susceptible infections: Infants <3 months: Oral: 30 mg/kg/day divided every 12 hours using the 125 mg/5 mL suspension
Lower respiratory tract infections, severe infections, sinusitis: Children ≥ 3 months and <40 kg: Oral: 45 mg/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours
Mild-to-moderate infections: Children ≥ 3 months and <40 kg: Oral: 25 mg/kg/day divided every 12 hours or 20 mg/kg/day divided every 8 hours
Otitis media (Augmentin ES-600®): Children ≥ 3 months and <40 kg: Oral: 90 mg/kg/day divided every 12 hours for 10 days in children with severe illness and when coverage for ß-lactamase positive H. influenzae and M. catarrhalis is needed.
Children >40 kg: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Clcr <30 mL/minute: Do not use 875 mg tablet or extended release tablets.
Clcr 10-30 mL/minute: 250-500 mg every 12 hours
Clcr <10 mL/minute: 250-500 every 24 hours
Hemodialysis: Moderately dialyzable (20% to 50%)
250-500 mg every 24 hours; administer dose during and after dialysis. Do not use extended release tablets.
Peritoneal dialysis: Moderately dialyzable (20% to 50%)
Amoxicillin: Administer 250 mg every 12 hours
Clavulanic acid: Dose for Clcr <10 mL/minute
Continuous arteriovenous or venovenous hemofiltration effects:
Amoxicillin: ~50 mg of amoxicillin/L of filtrate is removed
Clavulanic acid: Dose for Clcr <10 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL)
Amoclan:
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.14 mEq/5 mL; fruit flavor]
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.29 mEq/5 mL; fruit flavor]
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL) [contains phenylalanine 7 mg/5 mL, potassium 0.248 mEq/5 mL; orange flavor]
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.16 mEq/5 mL; banana flavor]
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.14 mEq/5 mL; orange flavor] [DSC]
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.32 mEq/5 mL; orange flavor]
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.29 mEq/5 mL; orange flavor] [DSC]
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.23 mEq/5 mL; strawberry cream flavor]
Tablet: 250: Amoxicillin 250 mg and clavulanate potassium 125 mg; 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
500: Amoxicillin 500 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
875: Amoxicillin 875 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg [contains phenylalanine]
Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg [contains potassium 12.6 mg (0.32 mEq) and sodium 29.3 mg (1.27 mEq) per tablet; packaged in either a 7-day or 10-day package]
DOSAGE FORMS: CONCISE
Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Amoclan:
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Tablet: 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg
500: Amoxicillin 500 mg and clavulanate potassium 125 mg
875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg
Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes extended release
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Administer with food to decrease stomach upset; shake suspension well before use. Extended release tablets should be administered with food.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
USE — Treatment of otitis media, sinusitis, and infections caused by susceptible organisms involving the lower respiratory tract, skin and skin structure, and urinary tract; spectrum same as amoxicillin with additional coverage of beta-lactamase producing B. catarrhalis, H. influenzae, N. gonorrhoeae, and S. aureus (not MRSA). The expanded coverage of this combination makes it a useful alternative when amoxicillin resistance is present and patients cannot tolerate alternative treatments.
ADVERSE REACTIONS SIGNIFICANT
>10%: Gastrointestinal: Diarrhea (3% to 34%; incidence varies upon dose and regimen used)
1% to 10%:
Dermatologic: Diaper rash, skin rash, urticaria
Gastrointestinal: Abdominal discomfort, loose stools, nausea, vomiting
Genitourinary: Vaginitis, vaginal mycosis
Miscellaneous: Moniliasis
<1% (Limited to important or life-threatening): Alkaline phosphatase increased, cholestatic jaundice, flatulence, headache, hepatic dysfunction, hepatitis, liver function tests increased, prothrombin time increased, thrombocytosis, vasculitis (hypersensitivity)
Additional adverse reactions seen with ampicillin-class antibiotics: Agitation, agranulocytosis, alkaline phosphatase increased, anaphylaxis, anemia, angioedema, anxiety, behavioral changes, bilirubin increased, black "hairy" tongue, confusion, convulsions, crystalluria, dizziness, enterocolitis, eosinophilia, erythema multiforme, exanthematous pustulosis, exfoliative dermatitis, gastritis, glossitis, hematuria, hemolytic anemia, hemorrhagic colitis, indigestion, insomnia, hyperactivity, interstitial nephritis, leukopenia, mucocutaneous candidiasis, pruritus, pseudomembranous colitis, serum sickness-like reaction, Stevens-Johnson syndrome, stomatitis, transaminases increased, thrombocytopenia, thrombocytopenic purpura, tooth discoloration, toxic epidermal necrolysis
CONTRAINDICATIONS — Hypersensitivity to amoxicillin, clavulanic acid, penicillin, or any component of the formulation; history of cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanate potassium therapy; Augmentin XR™ : severe renal impairment (Clcr <30 mL/minute) and hemodialysis patients
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Low incidence of cross-allergy with cephalosporins exists. Diarrhea: Incidence of diarrhea is higher than with amoxicillin alone. Hepatic effects: Although rare, hepatic dysfunction is more common in elderly and/or males, and occurs more frequently with prolonged treatment, and may occur after therapy is complete. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hepatic impairment: Use with caution in patients with hepatic impairment. Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Dosage form specific issues: Clavulanic acid content: Due to differing content of clavulanic acid, not all formulations are interchangeable. Phenylalanine: Some products contain phenylalanine.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, amoxicillin/clavulanate is classified as pregnancy category B. Both amoxicillin and clavulanic acid cross the placenta. There is no documented increased risk of teratogenic effects caused by amoxicillin/clavulanate. A potential increased risk of necrotizing enterocolitis in the newborn has been noted after maternal use of amoxicillin/clavulanate for preterm labor or premature prolonged rupture of membranes. When used during pregnancy, pharmacokinetic changes have been observed with amoxicillin alone (refer to the Amoxicillin monograph for details).
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Amoxicillin is found in breast milk. The manufacturer recommends that caution be used if administered to breast-feeding women. The use of amoxicillin/clavulanate may be safe while breast-feeding; however, the risk of adverse events in the infant may be increased when compared to the use of amoxicillin alone. The risk of adverse events may be related to maternal dose. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant.
DIETARY CONSIDERATIONS — May be taken with meals or on an empty stomach; take with meals to increase absorption and decrease GI intolerance; may mix with milk, formula, or juice. Extended release tablets should be taken with food. Some products contain phenylalanine. If you have phenylketonuria or PKU, avoid use. All dosage forms contain potassium.
PRICING — (data from drugstore.com)
Chewable (Amoxicillin-Pot Clavulanate)
400-57 mg (20): $63.79
Suspension (reconstituted) (Amoxicillin-Pot Clavulanate)
600-42.9 mg/5 mL (75): $35.99
Tablet, 12-hour (Augmentin XR)
1000-62.5 mg (28): $116.70
Tablets (Amoxicillin-Pot Clavulanate)
250-125 mg (30): $116.54
500-125 mg (20): $45.99
875-125 mg (20): $31.99
Tablets (Augmentin)
250-125 mg (30): $118.99
500-125 mg (30): $166.71
875-125 mg (20): $145.99
MONITORING PARAMETERS — Assess patient at beginning and throughout therapy for infection; with prolonged therapy, monitor renal, hepatic, and hematologic function periodically; monitor for signs of anaphylaxis during first dose
CANADIAN BRAND NAMES — Alti-Amoxi-Clav; Apo-Amoxi-Clav®; Augmentin®; Clavulin®; Novo-Clavamoxin; ratio-Aclavulanate
INTERNATIONAL BRAND NAMES — Acarbixin (MX); Aclam (ID); Ambilan (PE); AMK (TH); Amobay Cl (MX); Amocla (KP); Amocla Duo (KP); Amoclan (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amoclav (DE); Amoksiclav (TH); Amoksiklav (CL, PL); Amolanic (KP); Amolanic Duo (KP); Amoxa (KP); Amoxi Plus (PY); Amoxiclav (MX); Amoxiclav-BID (MX); Amoxiclav-Teva (IL); Amoxsiklav Forte (TH); Amoxxlin (KP); Amoxyclav (IL); Augamox (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); AugMaxcil (ZA); Augmentan (DE); Augmentin (AE, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, OM, PA, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TH, TN, TR, TT, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Augmentine (ES); Augmex (PH); Augpen (TH); Augurcin (PH); Bactiv (PH); Bactoclav (PH); Bioclavid (AE, BH, CY, DE, DK, EG, IL, IQ, IR, JO, KW, LB, LY, OM, PH, QA, SA, SE, SY, YE); Bioclavid Forte (PH); Cavumox (MY, TH); Cax (PH); Clacillin Duo Dry Syrup (KP); Clamax (KP); Clamentin (ZA); Clamohexal (AU); Clamohexal Duo (AU); Clamovid (HK, MY, SG); Clamoxin (MX); Clamoxyl (AU); Clamoxyl Duo 400 (AU); Clamoxyl DuoForte (AU); Clavamox (DE, ID, IN); Clavant (MX); Clavar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Claventin (IL); Clavinex (CN, EC); Clavipen (MX); Clavmex (PH); Clavodar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Clavoxil (BR); Clavoxine (EC); Clavucyd (MX); Clavulin (BF, BJ, CI, CO, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, MX, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Clavulin Duo Forte (AU); Clavulox Duo (AR, PY); Clavumox (DE, PE, ZA); Clavuser (MX); Cramon Duo (KP); Curam (AU, CO, CR, DO, GT, HK, MY, NI, PA, PE, PL, SG, SV, TH, TW); Danoclav (ID); Darzitil Plus (AR); E-Moxclav (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Enhancin (SG); Exten (PH); Fleming (HK); Forcid (PL); Fugentin (SG); Fullicilina Plus (AR); Gimaclav (MX); Hibiotic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Klamonex (KP); Klavic (PH); Klavocin (PL); Kmoxilin (KP); Lansiclav (ID); Moxiclav (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Moxicle (KP, TH); Moxlin (MX); Natravox (PH); Novamox (BR); Nufaclav (ID); Penhance (PH); Quali-Mentin (HK); Ramoclav (PL); Ranclav (TH, ZA); Riclasip (MX); Servamox (MX); Sinufin (MX); Spektramox (SE); Sullivan (PH); Suplentin (PH); Synermox (NZ); Taromentin (PL); Velamox CL (PE); Vestaclav (MY); Viaclav (ID); Vulamox (CO, ID)
MECHANISM OF ACTION — Clavulanic acid binds and inhibits beta-lactamases that inactivate amoxicillin resulting in amoxicillin having an expanded spectrum of activity. Amoxicillin inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS — Amoxicillin pharmacokinetics are not affected by clavulanic acid.
Amoxicillin: See Amoxicillin monograph.
Clavulanic acid:
Protein binding: ~25%
Metabolism: Hepatic
Half-life elimination: 1 hour
Time to peak: 1 hour
Excretion: Urine (30% to 40% as unchanged drug)
PATIENT INFORMATION — Take entire course of medication. Take extended release tablets with food. Report diarrhea promptly. Females should report onset of symptoms of candidal vaginitis
Sound-alike/look-alike issues:
Augmentin® may be confused with Azulfidine®
U.S. BRAND NAMES — Amoclan; Augmentin ES-600®; Augmentin XR®; Augmentin®
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS — Note: Dose is based on the amoxicillin component; see "Augmentin® Product-Specific Considerations" table.
Susceptible infections: Children >40 kg and Adults: Oral: 250-500 mg every 8 hours or 875 mg every 12 hours
Augmentin® Product-Specific Considerations
125 mg: Chewable tablet: q8h dosing Suspension:
" q8h dosing
" For adults having difficulty swallowing tablets, 125 mg/5 mL suspension may be substituted for 500 mg tablet.
200 mg: Chewable tablet:
" q12h dosing
" Contains phenylalanine Suspension:
" q12h dosing
" For adults having difficulty swallowing tablets, 200 mg/5 mL suspension may be substituted for 875 mg tablet.
250 mg: Chewable tablet:
" q8h dosing
" Contains phenylalanine
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid. Suspension:
" q8h dosing
" For adults having difficulty swallowing tablets, 250 mg/5 mL suspension may be substituted for 500 mg tablet. Tablet:
" q8h dosing
" Not for use in patients <40 kg
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid.
400 mg: Chewable tablet:
" q12h dosing
" Contains phenylalanine Suspension:
" q12h dosing
" For adults having difficulty swallowing tablets, 400 mg/5 mL suspension may be substituted for 875 mg tablet.
500 mg: Tablet: q8h or q12h dosing
600 mg: Suspension:
" q12h dosing
" Not for use in adults or children ≥ 40 kg
" 600 mg/5 mL suspension is not equivalent to or interchangeable with 200 mg/5 mL or 400 mg/5 mL due to differences in clavulanic acid.
875 mg: Tablet:
" q12h dosing
" Not for use in Clcr <30 mL/minute
1000 mg: Extended release tablet:
" q12h dosing
" Not for use in children <16 years of age
" Not interchangeable with two 500 mg tablets
" Not for use if Clcr <30 mL/minute or hemodialysis
Acute bacterial sinusitis: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 10 days
Bite wounds (animal/human): Oral: 875 mg every 12 hours or 500 mg every 8 hours
Chronic obstructive pulmonary disease: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Diabetic foot: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-14 days
Diverticulitis, perirectal abscess: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days
Erysipelas: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Febrile neutropenia: Oral: 875 mg every 12 hours
Pneumonia:
Aspiration: Oral: 875 mg every 12 hours
Community-acquired: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days
Pyelonephritis (acute, uncomplicated): Oral: 875 mg every 12 hours or 500 mg every 8 hours
Skin abscess: Oral: 875 mg every 12 hours
DOSING: PEDIATRIC — Note: Dose is based on the amoxicillin component; see "Augmentin® Product-Specific Considerations" table.
(For additional information see "Amoxicillin and clavulanate potassium: Pediatric drug information")
Susceptible infections: Infants <3 months: Oral: 30 mg/kg/day divided every 12 hours using the 125 mg/5 mL suspension
Lower respiratory tract infections, severe infections, sinusitis: Children ≥ 3 months and <40 kg: Oral: 45 mg/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours
Mild-to-moderate infections: Children ≥ 3 months and <40 kg: Oral: 25 mg/kg/day divided every 12 hours or 20 mg/kg/day divided every 8 hours
Otitis media (Augmentin ES-600®): Children ≥ 3 months and <40 kg: Oral: 90 mg/kg/day divided every 12 hours for 10 days in children with severe illness and when coverage for ß-lactamase positive H. influenzae and M. catarrhalis is needed.
Children >40 kg: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Clcr <30 mL/minute: Do not use 875 mg tablet or extended release tablets.
Clcr 10-30 mL/minute: 250-500 mg every 12 hours
Clcr <10 mL/minute: 250-500 every 24 hours
Hemodialysis: Moderately dialyzable (20% to 50%)
250-500 mg every 24 hours; administer dose during and after dialysis. Do not use extended release tablets.
Peritoneal dialysis: Moderately dialyzable (20% to 50%)
Amoxicillin: Administer 250 mg every 12 hours
Clavulanic acid: Dose for Clcr <10 mL/minute
Continuous arteriovenous or venovenous hemofiltration effects:
Amoxicillin: ~50 mg of amoxicillin/L of filtrate is removed
Clavulanic acid: Dose for Clcr <10 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL)
Amoclan:
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.14 mEq/5 mL; fruit flavor]
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.29 mEq/5 mL; fruit flavor]
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL) [contains phenylalanine 7 mg/5 mL, potassium 0.248 mEq/5 mL; orange flavor]
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.16 mEq/5 mL; banana flavor]
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.14 mEq/5 mL; orange flavor] [DSC]
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.32 mEq/5 mL; orange flavor]
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.29 mEq/5 mL; orange flavor] [DSC]
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.23 mEq/5 mL; strawberry cream flavor]
Tablet: 250: Amoxicillin 250 mg and clavulanate potassium 125 mg; 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
500: Amoxicillin 500 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
875: Amoxicillin 875 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg [contains phenylalanine]
Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg [contains potassium 12.6 mg (0.32 mEq) and sodium 29.3 mg (1.27 mEq) per tablet; packaged in either a 7-day or 10-day package]
DOSAGE FORMS: CONCISE
Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Amoclan:
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Tablet: 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg
500: Amoxicillin 500 mg and clavulanate potassium 125 mg
875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg
Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes extended release
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Administer with food to decrease stomach upset; shake suspension well before use. Extended release tablets should be administered with food.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
USE — Treatment of otitis media, sinusitis, and infections caused by susceptible organisms involving the lower respiratory tract, skin and skin structure, and urinary tract; spectrum same as amoxicillin with additional coverage of beta-lactamase producing B. catarrhalis, H. influenzae, N. gonorrhoeae, and S. aureus (not MRSA). The expanded coverage of this combination makes it a useful alternative when amoxicillin resistance is present and patients cannot tolerate alternative treatments.
ADVERSE REACTIONS SIGNIFICANT
>10%: Gastrointestinal: Diarrhea (3% to 34%; incidence varies upon dose and regimen used)
1% to 10%:
Dermatologic: Diaper rash, skin rash, urticaria
Gastrointestinal: Abdominal discomfort, loose stools, nausea, vomiting
Genitourinary: Vaginitis, vaginal mycosis
Miscellaneous: Moniliasis
<1% (Limited to important or life-threatening): Alkaline phosphatase increased, cholestatic jaundice, flatulence, headache, hepatic dysfunction, hepatitis, liver function tests increased, prothrombin time increased, thrombocytosis, vasculitis (hypersensitivity)
Additional adverse reactions seen with ampicillin-class antibiotics: Agitation, agranulocytosis, alkaline phosphatase increased, anaphylaxis, anemia, angioedema, anxiety, behavioral changes, bilirubin increased, black "hairy" tongue, confusion, convulsions, crystalluria, dizziness, enterocolitis, eosinophilia, erythema multiforme, exanthematous pustulosis, exfoliative dermatitis, gastritis, glossitis, hematuria, hemolytic anemia, hemorrhagic colitis, indigestion, insomnia, hyperactivity, interstitial nephritis, leukopenia, mucocutaneous candidiasis, pruritus, pseudomembranous colitis, serum sickness-like reaction, Stevens-Johnson syndrome, stomatitis, transaminases increased, thrombocytopenia, thrombocytopenic purpura, tooth discoloration, toxic epidermal necrolysis
CONTRAINDICATIONS — Hypersensitivity to amoxicillin, clavulanic acid, penicillin, or any component of the formulation; history of cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanate potassium therapy; Augmentin XR™ : severe renal impairment (Clcr <30 mL/minute) and hemodialysis patients
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Low incidence of cross-allergy with cephalosporins exists. Diarrhea: Incidence of diarrhea is higher than with amoxicillin alone. Hepatic effects: Although rare, hepatic dysfunction is more common in elderly and/or males, and occurs more frequently with prolonged treatment, and may occur after therapy is complete. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hepatic impairment: Use with caution in patients with hepatic impairment. Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Dosage form specific issues: Clavulanic acid content: Due to differing content of clavulanic acid, not all formulations are interchangeable. Phenylalanine: Some products contain phenylalanine.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, amoxicillin/clavulanate is classified as pregnancy category B. Both amoxicillin and clavulanic acid cross the placenta. There is no documented increased risk of teratogenic effects caused by amoxicillin/clavulanate. A potential increased risk of necrotizing enterocolitis in the newborn has been noted after maternal use of amoxicillin/clavulanate for preterm labor or premature prolonged rupture of membranes. When used during pregnancy, pharmacokinetic changes have been observed with amoxicillin alone (refer to the Amoxicillin monograph for details).
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Amoxicillin is found in breast milk. The manufacturer recommends that caution be used if administered to breast-feeding women. The use of amoxicillin/clavulanate may be safe while breast-feeding; however, the risk of adverse events in the infant may be increased when compared to the use of amoxicillin alone. The risk of adverse events may be related to maternal dose. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant.
DIETARY CONSIDERATIONS — May be taken with meals or on an empty stomach; take with meals to increase absorption and decrease GI intolerance; may mix with milk, formula, or juice. Extended release tablets should be taken with food. Some products contain phenylalanine. If you have phenylketonuria or PKU, avoid use. All dosage forms contain potassium.
PRICING — (data from drugstore.com)
Chewable (Amoxicillin-Pot Clavulanate)
400-57 mg (20): $63.79
Suspension (reconstituted) (Amoxicillin-Pot Clavulanate)
600-42.9 mg/5 mL (75): $35.99
Tablet, 12-hour (Augmentin XR)
1000-62.5 mg (28): $116.70
Tablets (Amoxicillin-Pot Clavulanate)
250-125 mg (30): $116.54
500-125 mg (20): $45.99
875-125 mg (20): $31.99
Tablets (Augmentin)
250-125 mg (30): $118.99
500-125 mg (30): $166.71
875-125 mg (20): $145.99
MONITORING PARAMETERS — Assess patient at beginning and throughout therapy for infection; with prolonged therapy, monitor renal, hepatic, and hematologic function periodically; monitor for signs of anaphylaxis during first dose
CANADIAN BRAND NAMES — Alti-Amoxi-Clav; Apo-Amoxi-Clav®; Augmentin®; Clavulin®; Novo-Clavamoxin; ratio-Aclavulanate
INTERNATIONAL BRAND NAMES — Acarbixin (MX); Aclam (ID); Ambilan (PE); AMK (TH); Amobay Cl (MX); Amocla (KP); Amocla Duo (KP); Amoclan (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amoclav (DE); Amoksiclav (TH); Amoksiklav (CL, PL); Amolanic (KP); Amolanic Duo (KP); Amoxa (KP); Amoxi Plus (PY); Amoxiclav (MX); Amoxiclav-BID (MX); Amoxiclav-Teva (IL); Amoxsiklav Forte (TH); Amoxxlin (KP); Amoxyclav (IL); Augamox (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); AugMaxcil (ZA); Augmentan (DE); Augmentin (AE, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, OM, PA, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TH, TN, TR, TT, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Augmentine (ES); Augmex (PH); Augpen (TH); Augurcin (PH); Bactiv (PH); Bactoclav (PH); Bioclavid (AE, BH, CY, DE, DK, EG, IL, IQ, IR, JO, KW, LB, LY, OM, PH, QA, SA, SE, SY, YE); Bioclavid Forte (PH); Cavumox (MY, TH); Cax (PH); Clacillin Duo Dry Syrup (KP); Clamax (KP); Clamentin (ZA); Clamohexal (AU); Clamohexal Duo (AU); Clamovid (HK, MY, SG); Clamoxin (MX); Clamoxyl (AU); Clamoxyl Duo 400 (AU); Clamoxyl DuoForte (AU); Clavamox (DE, ID, IN); Clavant (MX); Clavar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Claventin (IL); Clavinex (CN, EC); Clavipen (MX); Clavmex (PH); Clavodar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Clavoxil (BR); Clavoxine (EC); Clavucyd (MX); Clavulin (BF, BJ, CI, CO, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, MX, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Clavulin Duo Forte (AU); Clavulox Duo (AR, PY); Clavumox (DE, PE, ZA); Clavuser (MX); Cramon Duo (KP); Curam (AU, CO, CR, DO, GT, HK, MY, NI, PA, PE, PL, SG, SV, TH, TW); Danoclav (ID); Darzitil Plus (AR); E-Moxclav (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Enhancin (SG); Exten (PH); Fleming (HK); Forcid (PL); Fugentin (SG); Fullicilina Plus (AR); Gimaclav (MX); Hibiotic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Klamonex (KP); Klavic (PH); Klavocin (PL); Kmoxilin (KP); Lansiclav (ID); Moxiclav (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Moxicle (KP, TH); Moxlin (MX); Natravox (PH); Novamox (BR); Nufaclav (ID); Penhance (PH); Quali-Mentin (HK); Ramoclav (PL); Ranclav (TH, ZA); Riclasip (MX); Servamox (MX); Sinufin (MX); Spektramox (SE); Sullivan (PH); Suplentin (PH); Synermox (NZ); Taromentin (PL); Velamox CL (PE); Vestaclav (MY); Viaclav (ID); Vulamox (CO, ID)
MECHANISM OF ACTION — Clavulanic acid binds and inhibits beta-lactamases that inactivate amoxicillin resulting in amoxicillin having an expanded spectrum of activity. Amoxicillin inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS — Amoxicillin pharmacokinetics are not affected by clavulanic acid.
Amoxicillin: See Amoxicillin monograph.
Clavulanic acid:
Protein binding: ~25%
Metabolism: Hepatic
Half-life elimination: 1 hour
Time to peak: 1 hour
Excretion: Urine (30% to 40% as unchanged drug)
PATIENT INFORMATION — Take entire course of medication. Take extended release tablets with food. Report diarrhea promptly. Females should report onset of symptoms of candidal vaginitis
Amoxicillin
EDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amoxicillin may be confused with amoxapine, Amoxil®, Atarax®
Amoxil® may be confused with amoxapine, amoxicillin
International issues:
Fisamox® [Australia] may be confused with Fosamax® which is a brand name for alendronate in the U.S.
Fisamox® [Australia] may be confused with Vigamox® which is a brand name for moxifloxacin in the U.S.
U.S. BRAND NAMES — Amoxil®; Moxatag™
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS
Usual dosage range: Oral: 250-500 mg every 8 hours or 500-875 mg twice daily or extended-release tablet 775 mg once daily
Anthrax exposure (CDC guidelines): Oral: Note: Postexposure prophylaxis in pregnant or nursing women only with documented susceptible organisms: 500 mg every 8 hours
Ear, nose, throat, genitourinary tract, or skin/skin structure infections:
Mild-to-moderate: Oral: 500 mg every 12 hours or 250 mg every 8 hours
Severe: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Tonsillitis and/or pharyngitis: Oral: Extended release tablet: 775 mg once daily
Helicobacter pylorieradication: Oral: 1000 mg twice daily; requires combination therapy with at least one other antibiotic and an acid-suppressing agent (proton pump inhibitor or H2 blocker)
Lower respiratory tract infections: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Lyme disease: Oral: 500 mg every 6-8 hours (depending on size of patient) for 21-30 days
Prophylaxis against infective endocarditis: Oral: 2 g 30-60 minutes before procedure. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Prophylaxis in total joint replacement patients undergoing dental procedures which produce bacteremia: 2 g 1 hour prior to procedure
DOSING: PEDIATRIC
(For additional information see "Amoxicillin: Pediatric drug information")
Usual dosage range:
Children ≤ 3 months: Oral: 20-30 mg/kg/day divided every 12 hours
Children >3 months and <40 kg: Oral: 20-50 mg/kg/day in divided doses every 8-12 hours
Children ≥ 12 years: Oral: Extended-release tablet: 775 mg once daily
Acute otitis media: Children >3 months and <40 kg: Oral: 80-90 mg/kg/day divided every 12 hours
Anthrax exposure (CDC guidelines): Children >3 months and <40 kg: Oral: Note: Postexposure prophylaxis only with documented susceptible organisms: 80 mg/kg/day in divided doses every 8 hours (maximum: 500 mg/dose)
Community-acquired pneumonia:
4 months to <5 years: 80-100 mg/kg/day divided every 8 hours
5-15 years: 100 mg/kg/day divided every 8 hours; Note: Treatment with a macrolide or doxycycline (if age >8 years) is preferred due to higher prevalence of atypical pathogens in this age group
Ear, nose, throat, genitourinary tract, or skin/skin structure infections: Children >3 months and <40 kg: Oral:
Mild-to-moderate: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours
Severe: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours
Tonsillitis and/or pharyngitis: Children ≥ 12 years: Extended release tablet: 775 mg once daily
Lower respiratory tract infections: Children >3 months and <40 kg: Oral: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours
Lyme disease: Children >3 months and <40 kg: Oral: 25-50 mg/kg/day divided every 8 hours (maximum: 500 mg)
Prophylaxis against infective endocarditis: Children >3 months and <40 kg: Oral: 50 mg/kg 1 hour before procedure. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Use of certain dosage forms (eg, extended-release 775 mg tablet and immediate-release 875 mg tablet) should be avoided in patients with Clcr <30 mL/minute or patients requiring hemodialysis
Clcr 10-30 mL/minute: 250-500 mg every 12 hours
Clcr <10 mL/minute: 250-500 mg every 24 hours
Moderately dialyzable (20% to 50%) by hemodialysis or peritoneal dialysis; approximately 50 mg of amoxicillin per liter of filtrate is removed by continuous arteriovenous or venovenous hemofiltration. Dose as per Clcr <10 mL/minute guidelines.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 250 mg, 500 mg
Amoxil®: 500 mg [DSC]
Powder for suspension, oral: 125 mg/5 mL (80 mL, 100 mL, 150 mL); 200 mg/5 mL (50 mL, 75 mL, 100 mL); 250 mg/5 mL (80 mL, 100 mL, 150 mL); 400 mg/5 mL (50 mL, 75 mL, 100 mL)
Amoxil®: 250 mg/5 mL (100 mL, 150 mL) [contains sodium benzoate; bubble gum flavor] [DSC]; 400 mg/5 mL (100 mL) [contains sodium benzoate; bubble gum flavor] [DSC]
Powder for suspension, oral [drops]:
Amoxil®: 50 mg/mL (30 mL) [contains sodium benzoate; bubble gum flavor] [DSC]
Tablet: 500 mg, 875 mg
Tablet, chewable: 125 mg, 200 mg, 250 mg, 400 mg
Tablet, extended release:
Moxatag™ : 775 mg
DOSAGE FORMS: CONCISE
Capsule: 250 mg, 500 mg
Powder for suspension, oral: 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL
Tablet: 500 mg, 875 mg
Tablet, chewable: 125 mg, 200 mg, 250 mg, 400 mg
Tablet, extended release:
Moxatag™ : 775 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes drops and extended-release formulation
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. The appropriate amount of suspension may be mixed with formula, milk, fruit juice, water, ginger ale, or cold drinks; administer dose immediately after mixing.
Moxatag™ extended release tablet: Administer within 1 hour of finishing a meal.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
USE — Treatment of otitis media, sinusitis, and infections caused by susceptible organisms involving the upper and lower respiratory tract, skin, and urinary tract; prophylaxis of infective endocarditis in patients undergoing surgical or dental procedures; as part of a multidrug regimen for H. pylori eradication
USE - UNLABELED / INVESTIGATIONAL — Postexposure prophylaxis for anthrax exposure with documented susceptible organisms
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Central nervous system: Agitation, anxiety, behavioral changes, confusion, dizziness, headache, hyperactivity (reversible), insomnia, seizure
Dermatologic: Acute exanthematous pustulosis, erythematous maculopapular rash, erythema multiforme, exfoliative dermatitis, hypersensitivity vasculitis, mucocutaneous candidiasis, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Gastrointestinal: Black hairy tongue, diarrhea, hemorrhagic colitis, nausea, pseudomembranous colitis, tooth discoloration (brown, yellow, or gray; rare), vomiting
Hematologic: Agranulocytosis, anemia, eosinophilia, hemolytic anemia, leukopenia,thrombocytopenia, thrombocytopenia purpura
Hepatic: Acute cytolytic hepatitis, ALT increased, AST increased, cholestatic jaundice, hepatic cholestasis
Renal: Crystalluria
Miscellaneous: Anaphylaxis, serum sickness-like reaction
CONTRAINDICATIONS — Hypersensitivity to amoxicillin, penicillin, other beta-lactams, or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended. In addition, use of certain dosage forms (eg, extended-release 775 mg tablet and immediate-release 875 mg tablet) should be avoided in patients with Clcr <30 mL/minute or patients requiring hemodialysis.
Dosage form specific issues: Phenylalanine: Chewable tablets contain phenylalanine.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, amoxicillin is classified as pregnancy category B. There is no documented increased risk of adverse pregnancy outcome or teratogenic effects caused by amoxicillin. It is the drug of choice for the treatment of chlamydial infections in pregnancy and for anthrax prophylaxis when penicillin susceptibility is documented.
Due to pregnancy-induced physiologic changes, amoxicillin clearance is increased during pregnancy resulting in lower concentrations and smaller AUCs. Oral ampicillin-class antibiotics are poorly-absorbed during labor.
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Very small amounts of amoxicillin are excreted in breast milk. The manufacturer recommends that caution be exercised when administering amoxicillin to nursing women. The AAP considers amoxicillin to be "usually compatible with breastfeeding." Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant.
DIETARY CONSIDERATIONS — May be taken with food. Amoxil® chewable contains phenylalanine 1.82 mg per 200 mg tablet, phenylalanine 3.64 mg per 400 mg tablet.
Moxatag™ : Take within 1 hour of finishing a meal.
PRICING — (data from drugstore.com)
Capsules (Amoxicillin)
250 mg (90): $17.99
500 mg (30): $13.99
Capsules (Amoxil)
500 mg (30): $15.99
Chewable (Amoxicillin)
125 mg (21): $11.99
250 mg (30): $13.99
Chewable (Amoxil)
400 mg (20): $13.99
Suspension (reconstituted) (Amoxicillin)
250 mg/5 mL (150): $14.00
400 mg/5 mL (100): $16.99
Suspension (reconstituted) (Amoxil)
50 mg/mL (30): $8.99
200 mg/5 mL (100): $11.99
250 mg/5 mL (100): $8.99
250 mg/5 mL (150): $8.99
400 mg/5 mL (50): $8.99
400 mg/5 mL (75): $9.99
400 mg/5 mL (100): $11.99
Suspension (reconstituted) (Trimox)
125 mg/5 mL (100): $11.99
250 mg/5 mL (80): $11.99
Tablet, 24-hour (Moxatag)
775 mg (30): $249.98
Tablets (Amoxicillin)
500 mg (100): $49.99
875 mg (30): $26.99
Tablets (Amoxil)
500 mg (21): $12.99
875 mg (21): $27.99
MONITORING PARAMETERS — With prolonged therapy, monitor renal, hepatic, and hematologic function periodically; assess patient at beginning and throughout therapy for infection; monitor for signs of anaphylaxis during first dose
CANADIAN BRAND NAMES — Apo-Amoxi®; Gen-Amoxicillin; Lin-Amox; Mylan-Amoxicillin; Novamoxin®; Nu-Amoxi; PHL-Amoxicillin; PMS-Amoxicillin
INTERNATIONAL BRAND NAMES — Acilina (PY); Acimox (MX); Adbiotin (CO); Alfamox (IT); Almodan (GB); Almorsan (AR); Alphamox (AU); Amagesen Solutab (DE); Amicil (MX); Amimox (SE); Amobay (MX); Amoclave (ES); Amoclen (CZ); Amodex (FR); Amoflux (BR); Amohexal (AU); Amolin (JP, TW); Amosine (ID); Amotaks (PL); Amox (AE, BH, CY, EG, IL, IQ, IR, IT, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amoxa (HK); Amoxal (VE); Amoxapen (BB, BM, BS, BZ, GY, JM, NL, SG, SR, TT); Amoxcil (CL); Amoxcillin (TH); Amoxcin (TW); Amoxi (IL); Amoxi TO (TH); Amoxi-basan (DE); Amoxicap (PK); Amoxicilina (CO, EC); Amoxicilline (PL); Amoxiclin (PE); Amoxico (PH); Amoxidal (AR, UY); Amoxidin (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW); Amoxifur (MX); Amoxihexal (DE); Amoxil (AE, AU, BB, BF, BH, BJ, BM, BR, BS, BZ, CI, CY, EG, ET, GB, GH, GM, GN, GR, GY, ID, IE, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, NE, NG, NL, NZ, OM, PE, PL, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW); Amoxil Duo (AU); Amoxillin (IL, IT); Amoxin (FI); Amoxinova (MX); Amoxipen (IT); Amoxipenil (CN); Amoxisol (MX); Amoxivan (IN); Amoxivet (MX); Amoxsan (ID); Amoxsan Forte (ID); Amoxy-diolan (DE); Amoxycillin (PL); Amoxypen (DE, PE); Apo-Amoxi (MY, PL); Aroxin (SG); Azillin (CH); Bacihexal (PH); Bactamox (VE); Bactox (EE); Bactox Ge (FR); Baymox (HN); Beamoxy (MY); Bimxan (MX); Biotamoxal (AR); Bristamox (EC, FR); Bufamoxy (ID); Cilamox (AU, PH); Clamoxyl (AT, AU, BB, BE, BM, BS, BZ, CH, FR, GY, JM, JP, NL, PE, PT, SR, TT); Dimopen (MX); Duomox (BG, HN, PL); Dymoxin (TH); Efpinex (JP); Ethimox (ID); Farconcil (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Fisamox (AU); Flemoxin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Flubiotic (ES); Foxolin (KP); Fullcilina (AR); Gexcil (PH); Gimalxina (MX); Gomcillin (KP); Grinsul (AR); Grunamox (EC, PL); Hiconcil (BE, FR, ID, NL, PL); Hidramox (MX); Hipen (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Ibiamox (AE, AU, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, TH, YE); Ikamoxil (ID); Imacillin (DK, NO, SE); Imadrax (DK); Imaxilin (CO); Isimoxin (IT); Izoltil (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Jutamox (DE); Lamoxy (IN); Magnimox (PE); Manmox (TH); Maxamox (AU, NZ); Maxcil (ZA); Meixil (TH); Milamox-BIG (TH); Mopen (IT); Mox (IN); Moxacin (AU, NZ); Moxarin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Moxilen (BF, BJ, CI, ET, GH, GM, GN, HK, KE, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SG, SL, SN, TN, TW, TZ, UG, ZA, ZM, ZW); Moxitab (TH); Moxtid (ID); Moxylin (EC); Moxypen (IL, ZA); Moxyvit (IL); Novabritine (BE); Novamox (PH, PL); Novax (ID); Novoxil (BR); Ospamox (AE, AT, BG, BH, CY, DE, EG, HK, ID, IL, IQ, IR, JO, KW, LB, LY, NZ, OM, PE, PL, PT, QA, SA, SY, UY, YE); Pamocil (IT); Pamoxicillin (TW); Pamoxin (KP); Pasetocin (JP); Penamox (MX, NZ, PE); Penbiosyn (PH); Piramox (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Polymox (MX); Pondnoxcill (TH); Rancil (TH); Ranmoxy (AU, ZA); Ranoxyl (MY, TH); Robamox (ID); Sawacillin (JP); Sawamezin (JP); Servamox (TW); Setmoxil (HK); Shamoxil (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sia-mox (TH); Simoxil (IT); Solciclina (MX); Solpenox (ID); Sterimox (PH); Supercillin (TW); Teramoxyl (PH); Trifamox (AR, PY); Trimox (TH); Vastamox (PH); Velamox (PE); Widecillin (ID); Winpen (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Xalyn-Or (MX); Xazexy (PH); Yusimox (ID); Zamoxil (MY); Zerrsox (PH); Zimox (IT)
MECHANISM OF ACTION — Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS
Absorption: Oral: Rapid and nearly complete; food does not interfere
Extended-release tablet: Rate of absorption is slower compared to immediate-release formulations; food decreases the rate but not extent of absorption
Distribution: Widely to most body fluids and bone; poor penetration into cells, eyes, and across normal meninges
Pleural fluids, lungs, and peritoneal fluid; high urine concentrations are attained; also into synovial fluid, liver, prostate, muscle, and gallbladder; penetrates into middle ear effusions, maxillary sinus secretions, tonsils, sputum, and bronchial secretions
CSF:blood level ratio: Normal meninges: <1%; Inflamed meninges: 8% to 90%
Protein binding: 17% to 20%
Metabolism: Partially hepatic
Half-life elimination:
Neonates, full-term: 3.7 hours
Infants and Children: 1-2 hours
Adults: Normal renal function: 0.7-1.4 hours
Clcr <10 mL/minute: 7-21 hours
Time to peak: Capsule: 2 hours; Extended-release tablet: 3.1 hours; Suspension: 1 hour
Excretion: Urine (60% as unchanged drug); lower in neonatesNote: Extended-release tablets: In healthy volunteers, serum drug concentrations were below 0.25 mcg/mL and undetectable at 16 hours following dosing.
PATIENT INFORMATION — Take entire course of medication. Report diarrhea promptly. females should report symptoms of vaginitis. Pediatric drops may be placed on child's tongue or added to formula, milk, etc.
(For additional information see "Amoxicillin: Patient drug information")
PRODUCT AVAILABILITY
Moxatag™ : FDA approved January 2009; availability anticipated in March 2009
Moxatag™ is an extended-release tablet of amoxicillin intended for once-daily administration
Sound-alike/look-alike issues:
Amoxicillin may be confused with amoxapine, Amoxil®, Atarax®
Amoxil® may be confused with amoxapine, amoxicillin
International issues:
Fisamox® [Australia] may be confused with Fosamax® which is a brand name for alendronate in the U.S.
Fisamox® [Australia] may be confused with Vigamox® which is a brand name for moxifloxacin in the U.S.
U.S. BRAND NAMES — Amoxil®; Moxatag™
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS
Usual dosage range: Oral: 250-500 mg every 8 hours or 500-875 mg twice daily or extended-release tablet 775 mg once daily
Anthrax exposure (CDC guidelines): Oral: Note: Postexposure prophylaxis in pregnant or nursing women only with documented susceptible organisms: 500 mg every 8 hours
Ear, nose, throat, genitourinary tract, or skin/skin structure infections:
Mild-to-moderate: Oral: 500 mg every 12 hours or 250 mg every 8 hours
Severe: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Tonsillitis and/or pharyngitis: Oral: Extended release tablet: 775 mg once daily
Helicobacter pylorieradication: Oral: 1000 mg twice daily; requires combination therapy with at least one other antibiotic and an acid-suppressing agent (proton pump inhibitor or H2 blocker)
Lower respiratory tract infections: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Lyme disease: Oral: 500 mg every 6-8 hours (depending on size of patient) for 21-30 days
Prophylaxis against infective endocarditis: Oral: 2 g 30-60 minutes before procedure. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Prophylaxis in total joint replacement patients undergoing dental procedures which produce bacteremia: 2 g 1 hour prior to procedure
DOSING: PEDIATRIC
(For additional information see "Amoxicillin: Pediatric drug information")
Usual dosage range:
Children ≤ 3 months: Oral: 20-30 mg/kg/day divided every 12 hours
Children >3 months and <40 kg: Oral: 20-50 mg/kg/day in divided doses every 8-12 hours
Children ≥ 12 years: Oral: Extended-release tablet: 775 mg once daily
Acute otitis media: Children >3 months and <40 kg: Oral: 80-90 mg/kg/day divided every 12 hours
Anthrax exposure (CDC guidelines): Children >3 months and <40 kg: Oral: Note: Postexposure prophylaxis only with documented susceptible organisms: 80 mg/kg/day in divided doses every 8 hours (maximum: 500 mg/dose)
Community-acquired pneumonia:
4 months to <5 years: 80-100 mg/kg/day divided every 8 hours
5-15 years: 100 mg/kg/day divided every 8 hours; Note: Treatment with a macrolide or doxycycline (if age >8 years) is preferred due to higher prevalence of atypical pathogens in this age group
Ear, nose, throat, genitourinary tract, or skin/skin structure infections: Children >3 months and <40 kg: Oral:
Mild-to-moderate: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours
Severe: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours
Tonsillitis and/or pharyngitis: Children ≥ 12 years: Extended release tablet: 775 mg once daily
Lower respiratory tract infections: Children >3 months and <40 kg: Oral: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours
Lyme disease: Children >3 months and <40 kg: Oral: 25-50 mg/kg/day divided every 8 hours (maximum: 500 mg)
Prophylaxis against infective endocarditis: Children >3 months and <40 kg: Oral: 50 mg/kg 1 hour before procedure. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Use of certain dosage forms (eg, extended-release 775 mg tablet and immediate-release 875 mg tablet) should be avoided in patients with Clcr <30 mL/minute or patients requiring hemodialysis
Clcr 10-30 mL/minute: 250-500 mg every 12 hours
Clcr <10 mL/minute: 250-500 mg every 24 hours
Moderately dialyzable (20% to 50%) by hemodialysis or peritoneal dialysis; approximately 50 mg of amoxicillin per liter of filtrate is removed by continuous arteriovenous or venovenous hemofiltration. Dose as per Clcr <10 mL/minute guidelines.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 250 mg, 500 mg
Amoxil®: 500 mg [DSC]
Powder for suspension, oral: 125 mg/5 mL (80 mL, 100 mL, 150 mL); 200 mg/5 mL (50 mL, 75 mL, 100 mL); 250 mg/5 mL (80 mL, 100 mL, 150 mL); 400 mg/5 mL (50 mL, 75 mL, 100 mL)
Amoxil®: 250 mg/5 mL (100 mL, 150 mL) [contains sodium benzoate; bubble gum flavor] [DSC]; 400 mg/5 mL (100 mL) [contains sodium benzoate; bubble gum flavor] [DSC]
Powder for suspension, oral [drops]:
Amoxil®: 50 mg/mL (30 mL) [contains sodium benzoate; bubble gum flavor] [DSC]
Tablet: 500 mg, 875 mg
Tablet, chewable: 125 mg, 200 mg, 250 mg, 400 mg
Tablet, extended release:
Moxatag™ : 775 mg
DOSAGE FORMS: CONCISE
Capsule: 250 mg, 500 mg
Powder for suspension, oral: 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL
Tablet: 500 mg, 875 mg
Tablet, chewable: 125 mg, 200 mg, 250 mg, 400 mg
Tablet, extended release:
Moxatag™ : 775 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes drops and extended-release formulation
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. The appropriate amount of suspension may be mixed with formula, milk, fruit juice, water, ginger ale, or cold drinks; administer dose immediately after mixing.
Moxatag™ extended release tablet: Administer within 1 hour of finishing a meal.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
USE — Treatment of otitis media, sinusitis, and infections caused by susceptible organisms involving the upper and lower respiratory tract, skin, and urinary tract; prophylaxis of infective endocarditis in patients undergoing surgical or dental procedures; as part of a multidrug regimen for H. pylori eradication
USE - UNLABELED / INVESTIGATIONAL — Postexposure prophylaxis for anthrax exposure with documented susceptible organisms
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Central nervous system: Agitation, anxiety, behavioral changes, confusion, dizziness, headache, hyperactivity (reversible), insomnia, seizure
Dermatologic: Acute exanthematous pustulosis, erythematous maculopapular rash, erythema multiforme, exfoliative dermatitis, hypersensitivity vasculitis, mucocutaneous candidiasis, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Gastrointestinal: Black hairy tongue, diarrhea, hemorrhagic colitis, nausea, pseudomembranous colitis, tooth discoloration (brown, yellow, or gray; rare), vomiting
Hematologic: Agranulocytosis, anemia, eosinophilia, hemolytic anemia, leukopenia,thrombocytopenia, thrombocytopenia purpura
Hepatic: Acute cytolytic hepatitis, ALT increased, AST increased, cholestatic jaundice, hepatic cholestasis
Renal: Crystalluria
Miscellaneous: Anaphylaxis, serum sickness-like reaction
CONTRAINDICATIONS — Hypersensitivity to amoxicillin, penicillin, other beta-lactams, or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended. In addition, use of certain dosage forms (eg, extended-release 775 mg tablet and immediate-release 875 mg tablet) should be avoided in patients with Clcr <30 mL/minute or patients requiring hemodialysis.
Dosage form specific issues: Phenylalanine: Chewable tablets contain phenylalanine.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, amoxicillin is classified as pregnancy category B. There is no documented increased risk of adverse pregnancy outcome or teratogenic effects caused by amoxicillin. It is the drug of choice for the treatment of chlamydial infections in pregnancy and for anthrax prophylaxis when penicillin susceptibility is documented.
Due to pregnancy-induced physiologic changes, amoxicillin clearance is increased during pregnancy resulting in lower concentrations and smaller AUCs. Oral ampicillin-class antibiotics are poorly-absorbed during labor.
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Very small amounts of amoxicillin are excreted in breast milk. The manufacturer recommends that caution be exercised when administering amoxicillin to nursing women. The AAP considers amoxicillin to be "usually compatible with breastfeeding." Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant.
DIETARY CONSIDERATIONS — May be taken with food. Amoxil® chewable contains phenylalanine 1.82 mg per 200 mg tablet, phenylalanine 3.64 mg per 400 mg tablet.
Moxatag™ : Take within 1 hour of finishing a meal.
PRICING — (data from drugstore.com)
Capsules (Amoxicillin)
250 mg (90): $17.99
500 mg (30): $13.99
Capsules (Amoxil)
500 mg (30): $15.99
Chewable (Amoxicillin)
125 mg (21): $11.99
250 mg (30): $13.99
Chewable (Amoxil)
400 mg (20): $13.99
Suspension (reconstituted) (Amoxicillin)
250 mg/5 mL (150): $14.00
400 mg/5 mL (100): $16.99
Suspension (reconstituted) (Amoxil)
50 mg/mL (30): $8.99
200 mg/5 mL (100): $11.99
250 mg/5 mL (100): $8.99
250 mg/5 mL (150): $8.99
400 mg/5 mL (50): $8.99
400 mg/5 mL (75): $9.99
400 mg/5 mL (100): $11.99
Suspension (reconstituted) (Trimox)
125 mg/5 mL (100): $11.99
250 mg/5 mL (80): $11.99
Tablet, 24-hour (Moxatag)
775 mg (30): $249.98
Tablets (Amoxicillin)
500 mg (100): $49.99
875 mg (30): $26.99
Tablets (Amoxil)
500 mg (21): $12.99
875 mg (21): $27.99
MONITORING PARAMETERS — With prolonged therapy, monitor renal, hepatic, and hematologic function periodically; assess patient at beginning and throughout therapy for infection; monitor for signs of anaphylaxis during first dose
CANADIAN BRAND NAMES — Apo-Amoxi®; Gen-Amoxicillin; Lin-Amox; Mylan-Amoxicillin; Novamoxin®; Nu-Amoxi; PHL-Amoxicillin; PMS-Amoxicillin
INTERNATIONAL BRAND NAMES — Acilina (PY); Acimox (MX); Adbiotin (CO); Alfamox (IT); Almodan (GB); Almorsan (AR); Alphamox (AU); Amagesen Solutab (DE); Amicil (MX); Amimox (SE); Amobay (MX); Amoclave (ES); Amoclen (CZ); Amodex (FR); Amoflux (BR); Amohexal (AU); Amolin (JP, TW); Amosine (ID); Amotaks (PL); Amox (AE, BH, CY, EG, IL, IQ, IR, IT, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amoxa (HK); Amoxal (VE); Amoxapen (BB, BM, BS, BZ, GY, JM, NL, SG, SR, TT); Amoxcil (CL); Amoxcillin (TH); Amoxcin (TW); Amoxi (IL); Amoxi TO (TH); Amoxi-basan (DE); Amoxicap (PK); Amoxicilina (CO, EC); Amoxicilline (PL); Amoxiclin (PE); Amoxico (PH); Amoxidal (AR, UY); Amoxidin (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW); Amoxifur (MX); Amoxihexal (DE); Amoxil (AE, AU, BB, BF, BH, BJ, BM, BR, BS, BZ, CI, CY, EG, ET, GB, GH, GM, GN, GR, GY, ID, IE, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, NE, NG, NL, NZ, OM, PE, PL, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW); Amoxil Duo (AU); Amoxillin (IL, IT); Amoxin (FI); Amoxinova (MX); Amoxipen (IT); Amoxipenil (CN); Amoxisol (MX); Amoxivan (IN); Amoxivet (MX); Amoxsan (ID); Amoxsan Forte (ID); Amoxy-diolan (DE); Amoxycillin (PL); Amoxypen (DE, PE); Apo-Amoxi (MY, PL); Aroxin (SG); Azillin (CH); Bacihexal (PH); Bactamox (VE); Bactox (EE); Bactox Ge (FR); Baymox (HN); Beamoxy (MY); Bimxan (MX); Biotamoxal (AR); Bristamox (EC, FR); Bufamoxy (ID); Cilamox (AU, PH); Clamoxyl (AT, AU, BB, BE, BM, BS, BZ, CH, FR, GY, JM, JP, NL, PE, PT, SR, TT); Dimopen (MX); Duomox (BG, HN, PL); Dymoxin (TH); Efpinex (JP); Ethimox (ID); Farconcil (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Fisamox (AU); Flemoxin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Flubiotic (ES); Foxolin (KP); Fullcilina (AR); Gexcil (PH); Gimalxina (MX); Gomcillin (KP); Grinsul (AR); Grunamox (EC, PL); Hiconcil (BE, FR, ID, NL, PL); Hidramox (MX); Hipen (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Ibiamox (AE, AU, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, TH, YE); Ikamoxil (ID); Imacillin (DK, NO, SE); Imadrax (DK); Imaxilin (CO); Isimoxin (IT); Izoltil (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Jutamox (DE); Lamoxy (IN); Magnimox (PE); Manmox (TH); Maxamox (AU, NZ); Maxcil (ZA); Meixil (TH); Milamox-BIG (TH); Mopen (IT); Mox (IN); Moxacin (AU, NZ); Moxarin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Moxilen (BF, BJ, CI, ET, GH, GM, GN, HK, KE, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SG, SL, SN, TN, TW, TZ, UG, ZA, ZM, ZW); Moxitab (TH); Moxtid (ID); Moxylin (EC); Moxypen (IL, ZA); Moxyvit (IL); Novabritine (BE); Novamox (PH, PL); Novax (ID); Novoxil (BR); Ospamox (AE, AT, BG, BH, CY, DE, EG, HK, ID, IL, IQ, IR, JO, KW, LB, LY, NZ, OM, PE, PL, PT, QA, SA, SY, UY, YE); Pamocil (IT); Pamoxicillin (TW); Pamoxin (KP); Pasetocin (JP); Penamox (MX, NZ, PE); Penbiosyn (PH); Piramox (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Polymox (MX); Pondnoxcill (TH); Rancil (TH); Ranmoxy (AU, ZA); Ranoxyl (MY, TH); Robamox (ID); Sawacillin (JP); Sawamezin (JP); Servamox (TW); Setmoxil (HK); Shamoxil (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sia-mox (TH); Simoxil (IT); Solciclina (MX); Solpenox (ID); Sterimox (PH); Supercillin (TW); Teramoxyl (PH); Trifamox (AR, PY); Trimox (TH); Vastamox (PH); Velamox (PE); Widecillin (ID); Winpen (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Xalyn-Or (MX); Xazexy (PH); Yusimox (ID); Zamoxil (MY); Zerrsox (PH); Zimox (IT)
MECHANISM OF ACTION — Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS
Absorption: Oral: Rapid and nearly complete; food does not interfere
Extended-release tablet: Rate of absorption is slower compared to immediate-release formulations; food decreases the rate but not extent of absorption
Distribution: Widely to most body fluids and bone; poor penetration into cells, eyes, and across normal meninges
Pleural fluids, lungs, and peritoneal fluid; high urine concentrations are attained; also into synovial fluid, liver, prostate, muscle, and gallbladder; penetrates into middle ear effusions, maxillary sinus secretions, tonsils, sputum, and bronchial secretions
CSF:blood level ratio: Normal meninges: <1%; Inflamed meninges: 8% to 90%
Protein binding: 17% to 20%
Metabolism: Partially hepatic
Half-life elimination:
Neonates, full-term: 3.7 hours
Infants and Children: 1-2 hours
Adults: Normal renal function: 0.7-1.4 hours
Clcr <10 mL/minute: 7-21 hours
Time to peak: Capsule: 2 hours; Extended-release tablet: 3.1 hours; Suspension: 1 hour
Excretion: Urine (60% as unchanged drug); lower in neonatesNote: Extended-release tablets: In healthy volunteers, serum drug concentrations were below 0.25 mcg/mL and undetectable at 16 hours following dosing.
PATIENT INFORMATION — Take entire course of medication. Report diarrhea promptly. females should report symptoms of vaginitis. Pediatric drops may be placed on child's tongue or added to formula, milk, etc.
(For additional information see "Amoxicillin: Patient drug information")
PRODUCT AVAILABILITY
Moxatag™ : FDA approved January 2009; availability anticipated in March 2009
Moxatag™ is an extended-release tablet of amoxicillin intended for once-daily administration
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